DOCSLIB.ORG

Mechanisms of Membrane Remodeling by Peripheral Proteins and Divalent Cations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mechanisms of Membrane Remodeling by Peripheral Proteins and Divalent Cations University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 Mechanisms of Membrane Remodeling by Peripheral Proteins and Divalent Cations Zheng Shi University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biophysics Commons, and the Physical Chemistry Commons Recommended Citation Shi, Zheng, "Mechanisms of Membrane Remodeling by Peripheral Proteins and Divalent Cations" (2015). Publicly Accessible Penn Dissertations. 2011. https://repository.upenn.edu/edissertations/2011 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2011 For more information, please contact [email protected]. Mechanisms of Membrane Remodeling by Peripheral Proteins and Divalent Cations Abstract Biological membranes undergo constant shape remodeling involving the formation of highly curved structures. As one of the most extensively studied membrane remodeling events, endocytosis is a ubiquitous eukaryotic membrane budding, vesiculation, and internalization process fulfilling numerous roles including compensation of membrane area increase after bursts of exocytosis. There are multiple independent endocytic pathways which differ by their speed as well as the proteins that are involved in. Bin/Amphiphysin/Rvs (BAR) domain proteins, such as endophilin, are responsible for sensing or generating membrane curvature in multiple endocytic pathways. In this dissertation, I elucidate the mechanisms of membrane remodeling through in vitro experimental studies with synthetic lipid bilayers. Firstly, I investigated the binding and assembly of endophilin on planar membranes. Endophilin was found to be attracted to the membrane through electrostatic forces and to subsequently oligomerize on the membrane with the help of the protein’s N-terminal helices. Next, I studied the mechanisms that govern membrane shape transitions induced by BAR domain proteins. The initiation of membrane curvature occurs at well-defined membrane tensions and protein surface densities. Importantly, the membrane budding and tubulation initiated by membrane tension reduction provides a mechanistic explanation for high speed endocytic pathways. The experimentally determined membrane shape stability diagram shows remarkable consistency with a three-parameter curvature instability model. Comparing different BAR domain proteins, the ability of three BAR domain proteins to generate high membrane curvature increases significantly from endophilin to amphiphysin, and to SNX9. The protein-protein attraction strength was identified as one of the most important factors that leads to the dramatic difference among these structurally similar proteins. Furthermore, I examined membrane interactions of α-synuclein, an intrinsically disordered protein whose aggregation is a hallmark of Parkinson’s disease. The binding of α-synuclein monomers was found to linearly expand the membrane area before the protein is able to induce membrane curvature. The area expansion is achieved by thinning of the bilayer. As I experimentally demonstrate, these features make α- synuclein a reporter of membrane tension as well as a promoter for endocytosis. Finally, I found that Ca2+ ions can induce membrane invaginations through the clustering of charged lipids, albeit less efficiently than BAR domain oteins.pr As I will discuss, this suggests an intriguing role of Ca2+ ions in the evolution of life. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Chemistry First Advisor Tobias Baumgart Keywords alpha Synuclein, BAR domain proteins, Divalent cations, Membrane curvature, Membrane dynamics, Protein membrane interactions Subject Categories Biophysics | Chemistry | Physical Chemistry This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/2011 MECHANISMS OF MEMBRANE REMODELING BY PERIPHERAL PROTEINS AND DIVALENT CATIONS Zheng Shi A DISSERTATION in Chemistry Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2015 Supervisor of Dissertation _____________________ Dr. Tobias Baumgart, Associate Professor of Chemistry Graduate Group Chairperson ______________________ Dr. Gary A. Molander, Hirschmann-Makineni Professor of Chemistry Dissertation Committee: Dr. Jeffery G. Saven, Professor of Chemistry Dr. Feng Gai, Edmund J. and Louise W. Kahn Endowed Term Professor of Chemistry Dr. E. Michael Ostap, Professor of Physiology MECHANISMS OF MEMBRANE REMODELING BY PERIPHERAL PROTEINS AND DIVALENT CATIONS COPYRIGHT 2015 Zheng Shi This work is licensed under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 License To view a copy of this license, visit http://creativecommons.org/licenses/by-ny-sa/2.0/ Dedicated to my parents and my sister For their unconditional love and support iii ACKNOWLEDGMENT First of all, I want to express my sincere gratitude to Professor Tobias Baumgart, who has helped me in every aspect possible through the last five years. He is the reason why I fell in love with biophysics and want to become a good scientist in the future. I simply couldn’t have asked for a better advisor. I want to thank my committee members, Professor Jeffery Saven, Professor Feng Gai, and Professor Michael Ostap, for their priceless time, comments, and encouragements. They motivated me to think deeper about my research and were there for me whenever I needed help. I want to thank everyone I have overlapped within the Baumgart Lab, for being amazing labmates and supportive friends. Particularly, I want to thank Dr. Tingting Wu, Zhiming Chen, Dr. Benjamin Capraro, and Dr. Katarzyna Jankowska. We collaborated on multiple fruitful projects and had the best time doing experiments together. I’m also grateful to Dr. Michael Heinrich, who trained me to use optical tweezers when I had little idea about how to carry out an experiment. I want to thank Dr. Chih-Jung Hsu and Dr. Wan-Ting Hsieh for being the nicest people I know and helping me in every way they could when I was new to the lab. I want to thank Ningwei Li, Jaclyn Robustelli, Dr. Zachary Graber, and Vinicius Ferreira for spending valuable time reading and commenting on my manuscripts and thesis chapters. I also want to thank Dr. Chen Zhu, Chun Liu, and Dr. Sanghamitra Deb for sharing and discussing ideas with me. I want to thank Professor Elizabeth Rhoades for her tremendous help with my α- synuclein projects. I also want to thank Professor Kathleen Stebe and Dr. Marcello Cavallaro for teaching me about liquid crystals, Professor Min Wu and Maohan Su for introducing me to FBP17. I also benefited from enlightening discussions with Professor Adam Cohen, Professor Ravi Radhakrishnan, Dr. Ramakrishnan Natesan, Ryan Bradley, Professor Jonathan Sachs, Mike Lacy, Professor James Petersson, Dr. Rebecca Wissner, John Ferrie, Professor Paul Janmey, Dr. David Slochower, Professor Tom Lubensky, Professor Wei Guo, Professor So-Jung Park, and Professor Zahra Fakhraai. I want to thank my friends at Penn Chemistry, particularly, Dr. Yu-Hsiu Wang, Dr. Zhengzheng Liao, Dr. Shi Liu, Chun-Wei Lin, Fan Zheng, Yanxin Wang, Fang Liu, Qingjie Luo, Xinle Liu, and Diomedes Saldana-Greco. They made gradschool much more fun than I thought it would to be. I will never forget the days when we went on road trips, got drunk, or had group studies together. I’m extremely grateful for my parents and my sister who have been spoiling me for more than 25 years. I know they will always be there for me and will always be proud of whatever small things I achieve. I feel bad for missing and sometimes even forgetting their birthdays and other important occasions in the past five years. I wish I will be able to visit them more frequently in the future. iv When writing his best seller ‘A Brief History of Time’, Stephen Hawking was famously warned that for every equation in the book, the readership would be halved. Therefore, at the end, I want to thank my future readers, for being a member of the special group of people who are willing to be tortured by some 90 equations in this thesis, it means a lot to me… v ABSTRACT MECHANISMS OF MEMBRANE REMODELING BY PERIPHERAL PROTEINS AND DIVALENT CATIONS Zheng Shi Tobias Baumgart Biological membranes undergo constant shape remodeling involving the formation of highly curved structures. As one of the most extensively studied membrane remodeling events, endocytosis is a ubiquitous eukaryotic membrane budding, vesiculation, and internalization process fulfilling numerous roles including compensation of membrane area increase after bursts of exocytosis. There are multiple independent endocytic pathways which differ by their speed as well as the proteins that are involved in. Bin/Amphiphysin/Rvs (BAR) domain proteins, such as endophilin, are responsible for sensing or generating membrane curvature in multiple endocytic pathways. In this dissertation, I elucidate the mechanisms of membrane remodeling through in vitro experimental studies with synthetic lipid bilayers. Firstly, I investigated the binding and assembly of endophilin on planar membranes. Endophilin was found to be attracted to the membrane through electrostatic forces and to subsequently oligomerize on the membrane with the help of the protein’s N-terminal helices. vi Next, I studied the mechanisms that govern membrane shape transitions induced by BAR domain proteins. The initiation of membrane curvature occurs at well-defined
Load more

Recommended publications
  • Overexpression of Salicylic Acid Carboxyl Methyltransferase (Cssamt1) Enhances Tolerance to Huanglongbing Disease in Wanjincheng Orange (Citrus Sinensis (L.) Osbeck)
    International Journal of Molecular Sciences Article Overexpression of Salicylic Acid Carboxyl Methyltransferase (CsSAMT1) Enhances Tolerance to Huanglongbing Disease in Wanjincheng Orange (Citrus sinensis (L.) Osbeck) Xiuping Zou * , Ke Zhao, Yunuo Liu, Meixia Du, Lin Zheng, Shuai Wang, Lanzhen Xu, Aihong Peng, Yongrui He, Qin Long and Shanchun Chen * Citrus Research Institute, Southwest University/Chinese Academy of Agricultural Sciences, Chongqing 400716, China; [email protected] (K.Z.); [email protected] (Y.L.); [email protected] (M.D.); [email protected] (L.Z.); [email protected] (S.W.); [email protected] (L.X.); [email protected] (A.P.); [email protected] (Y.H.); [email protected] (Q.L.) * Correspondence: [email protected] (X.Z.); [email protected] (S.C.) Abstract: Citrus Huanglongbing (HLB) disease or citrus greening is caused by Candidatus Liberibacter asiaticus (Las) and is the most devastating disease in the global citrus industry. Salicylic acid (SA) plays a central role in regulating plant defenses against pathogenic attack. SA methyltransferase (SAMT) modulates SA homeostasis by converting SA to methyl salicylate (MeSA). Here, we report on the functions of the citrus SAMT (CsSAMT1) gene from HLB-susceptible Wanjincheng orange Citation: Zou, X.; Zhao, K.; Liu, Y.; (Citrus sinensis (L.) Osbeck) in plant defenses against Las infection. The CsSAMT1 cDNA was Du, M.; Zheng, L.; Wang, S.; Xu, L.; expressed in yeast. Using in vitro enzyme assays, yeast expressing CsSAMT1 was confirmed to Peng, A.; He, Y.; Long, Q.; et al. specifically catalyze the formation of MeSA using SA as a substrate. Transgenic Wanjincheng orange Overexpression of Salicylic Acid plants overexpressing CsSAMT1 had significantly increased levels of SA and MeSA compared to Carboxyl Methyltransferase wild-type controls.
    [Show full text]
  • Mapping the Interface Between Calmodulin and MARCKS-Related Protein by Fluorescence Spectroscopy Andreas Ulrich*†‡, Arndt A
    Mapping the interface between calmodulin and MARCKS-related protein by fluorescence spectroscopy Andreas Ulrich*†‡, Arndt A. P. Schmitz*‡§, Thomas Braun*‡¶, Tao Yuanʈ‡, Hans J. Vogelʈ, and Guy Verge` res*,** *Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland; and ʈDepartment of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada Edited by H. Ronald Kaback, University of California, Los Angeles, CA, and approved March 3, 2000 (received for review November 16, 1999) MARCKS-related protein (MRP) is a myristoylated protein kinase C acid residues. The effector domain could be on the surface of substrate that binds calmodulin (CaM) with nanomolar affinity. To MARCKS proteins and partially exposed to water (model B). This obtain structural information on this protein, we have engineered model fits the proposed amphipathic structure of the effector 10 tryptophan residues between positions 89 and 104 in the domain (basic͞hydrophobic residues). Finally, the effector domain effector domain, a 24-residue-long amphipathic segment that could be completely exposed to water and either act as a hinge mediates binding of MRP to CaM. We show that the effector between the C- and N-terminal domains of MARCKS proteins domain is in a polar environment in free MRP, suggesting exposure (model C1) or form an exposed loop on the surface of the protein to water, in agreement with a rod-shaped structure of the protein. (model C2). The observation that MARCKS proteins are elon- The effector domain participates in the binding of MRP to CaM, as gated molecules (5, 10) supports model C1.
    [Show full text]
  • Supplementary Figure S1 Functional Characterisation of Snmp:GFP
    doi: 10.1038/nature06328 SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURE LEGENDS Figure S1 | Functional characterisation of SNMP fusion proteins. Dose-response curve for cVA in Or67d neurons of wild-type (Berlin), SNMP mutant (Or67d- GAL4/+;SNMP1/SNMP2), SNMP:GFP rescue (Or67d-GAL4/UAS- SNMP:GFP;SNMP1/SNMP2) and YFP(1):Or83b/SNMP:YFP(2) rescue (Or67d:GAL4,UAS-YFP(1):Or83b/UAS-SNMP:YFP(2);SNMP1,Or83b2/SNMP2,Or83b1 ) animals. Mean responses are plotted (± s.e.m; wild-type n=47, SNMP mutant n=46, SNMP:GFP rescue n=20; YFP(1):Or83b/SNMP:YFP(2) rescue n=22; ≤4 sensilla/animal, mixed genders). Wild-type and SNMP:GFP rescue responses to cVA are not significantly different (ANOVA; p>0.1175). YFP(1):Or83b/SNMP:YFP(2) rescue responses to cVA are highly significantly different from SNMP mutants and from wild- type (ANOVA; p<0.0001), indicating partial rescue. Figure S2 | Cell type-specific rescue of SNMP expression. a, Immunostaining for mCD8:GFP (anti-GFP, green) and LUSH (magenta) in LUSH-GAL4/UAS-mCD8:GFP animals reveals faithful recapitulation of endogenous expression by the LUSH-GAL4 driver. b, Two-colour RNA in situ hybridisation for SNMP (green) and Or67d (magenta) in antennal sections of wild-type, Or67d neuron SNMP rescue (Or67d-GAL4/UAS- SNMP;SNMP1/SNMP2) and support cell SNMP rescue (LUSH-GAL4/UAS- SNMP;SNMP1/SNMP2) animals. www.nature.com/nature 1 Benton et al., Figure S1 ) -1 wild-type 120 SNMP:GFP rescue 80 YFP(1):Or83b/SNMP:YFP(2) rescue 40 Corrected response (spikes s 0 SNMP-/- 0 0.1 1 10 100 cVA (%) www.nature.com/nature 2 Benton
    [Show full text]
  • Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Yazan H
    University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 8-2013 Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Yazan H. Akkam University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/etd Part of the Biochemistry Commons, Medicinal and Pharmaceutical Chemistry Commons, and the Molecular Biology Commons Recommended Citation Akkam, Yazan H., "Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications" (2013). Theses and Dissertations. 908. http://scholarworks.uark.edu/etd/908 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Cell and Molecular Biology by Yazan H. Akkam Jordan University of Science and Technology Bachelor of Science in Pharmacy, 2001 Al-Balqa Applied University Master of Science in Biochemistry and Chemistry of Pharmaceuticals, 2005 August 2013 University of Arkansas This dissertation is approved for recommendation to the Graduate Council. Dr. David S. McNabb Dissertation Director Professor Roger E. Koeppe II Professor Gisela F. Erf Committee Member Committee Member Professor Ralph L. Henry Dr. Suresh K. Thallapuranam Committee Member Committee Member ABSTRACT Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs.
    [Show full text]
  • IRON-REGULATORY FUNCTION of HEPCIDIN in the CHANNEL CATFISH and WESTERN CLAWED FROG Except Where Reference Is Made to the Work
    IRON-REGULATORY FUNCTION OF HEPCIDIN IN THE CHANNEL CATFISH AND WESTERN CLAWED FROG Except where reference is made to the work of others, the work described in this dissertation is my own or was done in collaboration with my advisory committee. This dissertation does not include proprietary or classified information. __________________________ Xueyou Hu Certificate of Approval: __________________________ __________________________ Jishu Shi, Co-Chair Edward E. Morrison, Co-Chair Assistant Professor Professor Anatomy, Physiology and Anatomy, Physiology and Pharmacology Pharmacology __________________________ __________________________ Robert J. Kemppainen Christine C. Dykstra Professor Associate Professor Anatomy, Physiology and Pathobiology Pharmacology __________________________ __________________________ Yingzi Cong Joe F. Pittman Assistant Professor Interim Dean Medicine Graduate School IRON-REGULATORY FUNCTION OF HEPCIDIN IN THE CHANNEL CATFISH AND WESTERN CLAWED FROG Xueyou Hu A Dissertation Submitted to the Graduate Faculty of Auburn University in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy Auburn, Alabama May 10, 2008 IRON-REGULATORY FUNCTION OF HEPCIDIN IN THE CHANNEL CATFISH AND WESTERN CLAWED FROG XUEYOU HU Permission is granted to Auburn University to make copies of this dissertation at its discretion, upon request of individuals or institutions at their expense. The author reserves all publication rights. ______________________________ Signature of Author ______________________________ Date
    [Show full text]
  • Regeneron Science Talent Search 2021 Scholars 2021 Scholars
    REGENERON SCIENCE TALENT SEARCH 2021 SCHOLARS 2021 SCHOLARS The Regeneron Science Talent Search (Regeneron STS), a program of Society for Science, is the nation’s most prestigious science and math competition for high school seniors. Alumni of STS have made extraordinary contributions to science and hold more than 100 of the world’s most distinguished science and math honors, including the Nobel Prize and the National Medal of Science. Each year, 300 Regeneron STS scholars and their schools are recognized. From that select pool of scholars, 40 student finalists are invited to participate in final judging, display their work to the public, meet with notable scientists and compete for awards, including the top award of $250,000. Regeneron Science Talent Search, A Program of Society for Science ARIZONA Scottsdale BASIS Scottsdale Mehta, Viraj, 18 GLIA-Deep: Glioblastoma Image Analysis Using Deep Learning Convolutional Neural Networks to Accurately Classify Gene Methylation and Predict Drug Effectiveness CALIFORNIA Arcadia Arcadia High School Liu, Stanley Cheung, 17 A Microfluidic Device for Blood Plasma Separation and Fluorescence Detection of Biomarkers Using Acoustic Microstreaming Atherton Menlo School Tung, Katherine, 17 The Sperner Property for 132-Avoiding Intervals in the Weak Order Cupertino Cupertino High School Agrawal, Vardhan, 18 BP-Lytic: A Novel Apparatus to Continuously, Cufflessly, and Affordably Monitor Blood Pressure Trends Homestead High School Sanyal, Anushka, 17 Intronic RNA Lariats Protect Against Neurodegenerative Disease
    [Show full text]
  • Optimizing Exogenous Surfactant As a Pulmonary Delivery Vehicle for Chicken Cathelicidin-2
    Lawrence Berkeley National Laboratory Recent Work Title Optimizing Exogenous Surfactant as a Pulmonary Delivery Vehicle for Chicken Cathelicidin-2. Permalink https://escholarship.org/uc/item/9bk2h47d Journal Scientific reports, 10(1) ISSN 2045-2322 Authors Baer, Brandon Veldhuizen, Edwin JA Molchanova, Natalia et al. Publication Date 2020-06-10 DOI 10.1038/s41598-020-66448-1 Peer reviewed eScholarship.org Powered by the California Digital Library University of California www.nature.com/scientificreports OPEN Optimizing Exogenous Surfactant as a Pulmonary Delivery Vehicle for Chicken Cathelicidin-2 Brandon Baer1 ✉ , Edwin J. A. Veldhuizen2, Natalia Molchanova3,4, Shehrazade Jekhmane5, Markus Weingarth5, Håvard Jenssen3, Jennifer S. Lin6, Annelise E. Barron6, Cory Yamashita1,7 & Ruud Veldhuizen1,7 The rising incidence of antibiotic-resistant lung infections has instigated a much-needed search for new therapeutic strategies. One proposed strategy is the use of exogenous surfactants to deliver antimicrobial peptides (AMPs), like CATH-2, to infected regions of the lung. CATH-2 can kill bacteria through a diverse range of antibacterial pathways and exogenous surfactant can improve pulmonary drug distribution. Unfortunately, mixing AMPs with commercially available exogenous surfactants has been shown to negatively impact their antimicrobial function. It was hypothesized that the phosphatidylglycerol component of surfactant was inhibiting AMP function and that an exogenous surfactant, with a reduced phosphatidylglycerol composition would increase peptide mediated killing at a distal site. To better understand how surfactant lipids interacted with CATH-2 and afected its function, isothermal titration calorimetry and solid-state nuclear magnetic resonance spectroscopy as well as bacterial killing curves against Pseudomonas aeruginosa were utilized. Additionally, the wet bridge transfer system was used to evaluate surfactant spreading and peptide transport.
    [Show full text]
  • Magainin 2 in Action: Distinct Modes of Membrane Permeabilization in Living Bacterial and Mammalian Cells
    Biophysical Journal Volume 95 December 2008 5757–5765 5757 Magainin 2 in Action: Distinct Modes of Membrane Permeabilization in Living Bacterial and Mammalian Cells Yuichi Imura, Naoki Choda, and Katsumi Matsuzaki Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-Ku, Kyoto 606-8501, Japan ABSTRACT Interactions of cationic antimicrobial peptides with living bacterial and mammalian cells are little understood, although model membranes have been used extensively to elucidate how peptides permeabilize membranes. In this study, the interaction of F5W-magainin 2 (GIGKWLHSAKKFGKAFVGEIMNS), an equipotent analogue of magainin 2 isolated from the African clawed frog Xenopus laevis, with unfixed Bacillus megaterium and Chinese hamster ovary (CHO)-K1 cells was investigated, using confocal laser scanning microscopy. A small amount of tetramethylrhodamine-labeled F5W-magainin 2 was incorporated into the unlabeled peptide for imaging. The influx of fluorescent markers of various sizes into the cytosol revealed that magainin 2 permeabilized bacterial and mammalian membranes in significantly different ways. The peptide formed pores with a diameter of ;2.8 nm (, 6.6 nm) in B. megaterium, and translocated into the cytosol. In contrast, the peptide significantly perturbed the membrane of CHO-K1 cells, permitting the entry of a large molecule (diameter, .23 nm) into the cytosol, accompanied by membrane budding and lipid flip-flop, mainly accumulating in mitochondria and nuclei. Adenosine triphosphate and negatively charged glycosaminoglycans were little involved in the magainin-induced permeabilization of membranes in CHO-K1 cells. Furthermore, the susceptibility of CHO-K1 cells to magainin was found to be similar to that of erythrocytes. Thus, the distinct membrane-permeabilizing processes of magainin 2 in bacterial and mammalian cells were, to the best of our knowledge, visualized and characterized in detail for the first time.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,829,086 B2 Hilbert Et Al
    US007829086B2 (12) United States Patent (10) Patent No.: US 7,829,086 B2 Hilbert et al. (45) Date of Patent: Nov. 9, 2010 (54) HUMANIZED ANTI-CD22 ANTIBODIES AND 2004/0202658 A1 10/2004 Benyunes THEIR USE IN TREATMENT OF 2004/021915.6 A1 11/2004 Goldenberg et al. ONCOLOGY, TRANSPLANTATION AND 2005, 0118182 A1 6/2005 Pastan et al. AUTOIMMUNE DISEASE 2007,0264260 A1 11/2007 Tuscano et al. (75) Inventors: David M. Hilbert, Bethesda, MD (US); 2008.0118505 A1 5/2008 Tedder Tarran Jones, Radlett (GB); David G. Williams, Epsom (GB) (73) Assignees: Medimmune, LLC, Gaithersburg, MD FOREIGN PATENT DOCUMENTS (US); Aeres Biomedical, Ltd., London EP O 660 721 B1 10, 2008 (GB) WO WOO3,O93320 A2 11/2003 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 132 days. OTHER PUBLICATIONS (21) Appl. No.: 11/715,308 MacCallum et al. (J. Mol. Biol. (1996) 262:732-745).* De Pascalis et al. (The Journal of Immunology (2002) 169, 3076 (22) Filed: Mar. 6, 2007 3084).* (65) Prior Publication Data Casset et al. (2003) BBRC 307, 198-205).* Vajdos et al. (2002) J. Mol. Biol. 320, 415-428).* US 2007/O258981 A1 Nov. 8, 2007 Holmetal ((2007) Mol. Immunol. 44: 1075-1084).* Related U.S. Application Data Chen et al. (J. Mol. Bio. (1999) 293, 865-881).* Wu et al. (J. Mol. Biol. (1999) 294, 151-162).* (60) Provisional application No. 60/779,806, filed on Mar. Brummell et al. (Biochemistry 32:1180-1187 (1993)).* 6, 2006.
    [Show full text]
  • A Master Autoantigen-Ome Links Alternative Splicing, Female Predilection, and COVID-19 to Autoimmune Diseases
    bioRxiv preprint doi: https://doi.org/10.1101/2021.07.30.454526; this version posted August 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. A Master Autoantigen-ome Links Alternative Splicing, Female Predilection, and COVID-19 to Autoimmune Diseases Julia Y. Wang1*, Michael W. Roehrl1, Victor B. Roehrl1, and Michael H. Roehrl2* 1 Curandis, New York, USA 2 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA * Correspondence: [email protected] or [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.30.454526; this version posted August 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Chronic and debilitating autoimmune sequelae pose a grave concern for the post-COVID-19 pandemic era. Based on our discovery that the glycosaminoglycan dermatan sulfate (DS) displays peculiar affinity to apoptotic cells and autoantigens (autoAgs) and that DS-autoAg complexes cooperatively stimulate autoreactive B1 cell responses, we compiled a database of 751 candidate autoAgs from six human cell types. At least 657 of these have been found to be affected by SARS-CoV-2 infection based on currently available multi-omic COVID data, and at least 400 are confirmed targets of autoantibodies in a wide array of autoimmune diseases and cancer.
    [Show full text]
  • Inducible Tolerance to Bacillus Thuringiensis (Bt) Endotoxins Based on Cell-Free Immune Reactions
    Inducible tolerance to Bacillus thuringiensis (Bt) endotoxins based on cell-free immune reactions by Mohammad Mahbubur Rahman B. Sc (Hons.) & M. Sc in Zoology (Dhaka University, Bangladesh) A thesis submitted for the degree of Doctor of Philosophy in the Faculty of Science at the University of Adelaide Discipline of Plant and Pest School of Agriculture, Food and Wine Waite Campus, Glen Osmond SA 5064, Australia November 2OO6 To my father Late M. Abdur Rahman TneL¡ or CoNTENTS Abstract I Statement iv Acknowledgements V Chapter One 1 Overview of the study Ghapter Two 12 Literature Review 1. General introduction 14 2. Literature review 15 2.1 Introduction 15 2.2 Bt-endotoxins (Cry-toxins) 16 2.2.1 Abriefhistory as biopesticídes 2.2.2 Host range and commercial products 2.2.3 Classification of Cry-toxins 2.2.4 Structure of Cry-toxins 2.2.5 Mode of action of Cry-toxins in insect midgut 2.2.6 Cry-toxin receptors in insect midgut 2.2.7 Pests resistant to Cry-toxins 2.2.8 Mechanisms of Cryloxins resistance in insects 2.3 Inducible tolerance to Bt Cry-toxins in insect pests 33 2.3.1 Introductíon 2.3.2 Inducibletolerancemechanisms 2.3.3 Insect immunity 2.3.4 Parasitoid-derivedimmunesuppressors 2.3.5 Mode of action of Cryloxíns in insect midgut 2.3.6 Cry-toxin receptors ín insect midgut 2.3.7 Pests resistant to Cry-toxins 2.3.8 Mechanisms of Cry-toxins resistance in insects 3. The aim of the study 41 4. Reference cited 43 Ghapter Three 60 Paper l: Cell-free immune reactions in insects Abstract 62 1.
    [Show full text]
  • Investigation of Morphological Changes of HPS Membrane Caused by Cecropin B Through Scanning Electron Microscopy and Atomic Forc
    J Vet Sci. 2021 Sep;22(5):e59 https://doi.org/10.4142/jvs.2021.22.e59 pISSN 1229-845X·eISSN 1976-555X Original Article Investigation of morphological changes Microbiology of HPS membrane caused by cecropin B through scanning electron microscopy and atomic force microscopy Han Hu 1,2,†, Changsheng Jiang 2,†, Binzhou Zhang 2, Nan Guo 2, Zhonghua Li 2, Xiaozhen Guo 2, Yang Wang ,1 Binlei Liu 1, Qigai He 2,* 1National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, Hubei 430068, China 2State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China Received: Jan 22, 2021 ABSTRACT Revised: Jun 2, 2021 Accepted: Jun 4, 2021 Published online: Jul 7, 2021 Background: Antimicrobial peptides (AMPs) have been identified as promising compounds for consideration as novel antimicrobial agents. *Corresponding author: Objectives: This study analyzed the efficacy of cecropin B againstHaemophilus parasuis isolates Qigai He through scanning electron microscopy (SEM) and atomic force microscopy (AFM) experiments. State Key Laboratory of Agricultural Results: Microbiology, College of Veterinary Medicine, Cecropin B exhibited broad inhibition activity against 15 standard Haemophilus Huazhong Agricultural University, No. 1 parasuis (HPS) strains and 5 of the clinical isolates had minimum inhibition concentrations Shizishan Street, Hongshan District, Wuhan, (MICs) ranging from 2 to 16 μg/mL. Microelectrophoresis and hexadecane adsorption assays Hubei 430070, China. indicated that the more hydrophobic and the higher the isoelectric point (IEP) of the strain, E-mail: [email protected] the more sensitive it was to cecropin B.
    [Show full text]