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1W9c Lichtarge Lab 2006 Pages 1–7 1w9c Evolutionary trace report by report maker June 18, 2010 4.3.1 Alistat 7 4.3.2 CE 7 4.3.3 DSSP 7 4.3.4 HSSP 7 4.3.5 LaTex 7 4.3.6 Muscle 7 4.3.7 Pymol 7 4.4 Note about ET Viewer 7 4.5 Citing this work 7 4.6 About report maker 7 4.7 Attachments 7 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 1w9c): Title: Proteolytic fragment of crm1 spanning six c-terminal heat repeats Compound: Mol id: 1; molecule: crm1 protein; chain: a, b; frag- ment: c-terminal six heat repeats, residues 707-1027; synonym: exportin 1; engineered: yes Organism, scientific name: Homo Sapiens; 1w9c contains a single unique chain 1w9cA (321 residues long) CONTENTS and its homologue 1w9cB. 1 Introduction 1 2 CHAIN 1W9CA 2.1 O14980 overview 2 Chain 1w9cA 1 2.1 O14980 overview 1 From SwissProt, id O14980, 100% identical to 1w9cA: 2.2 Multiple sequence alignment for 1w9cA 1 Description: Exportin-1 (Chromosome region maintenance 1 protein 2.3 Residue ranking in 1w9cA 2 homolog). 2.4 Top ranking residues in 1w9cA and their position on Organism, scientific name: Homo sapiens (Human). the structure 2 Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; 2.4.1 Clustering of residues at 25% coverage. 2 Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; 2.4.2 Overlap with known functional surfaces at Catarrhini; Hominidae; Homo. 25% coverage. 2 Function: Mediates the nuclear export of cellular proteins (cargoes) 2.4.3 Possible novel functional surfaces at 25% bearing a leucine-rich nuclear export signal (NES) and of RNAs. In coverage. 3 the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase Ran in its active GTP- 3 Notes on using trace results 5 bound form. Docking of this complex to the nuclear pore complex 3.1 Coverage 5 (NPC) is mediated through binding to nucleoporins. Upon transit 3.2 Known substitutions 6 of an nuclear export complex into the cytoplasm, disassembling of 3.3 Surface 6 the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by 3.4 Number of contacts 6 RANBP1 and RANGAP1, respectively) cause release of the cargo 3.5 Annotation 6 from the export receptor. The directionality of nuclear export is 3.6 Mutation suggestions 6 thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. 4 Appendix 6 Also mediates the nuclear export of the Rev protein of HIV-1 and 4.1 File formats 6 Rex protein of HTLV-1. Involved in Rex dimerization. Involved in 4.2 Color schemes used 6 U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late 4.3 Credits 7 precursor U3 snoRNA bearing a TMG cap. 1 Lichtarge lab 2006 Subunit: Found in a nuclear export complex with RANBP3 and Ran. Found in a complex with HIV-1 Rev, HIV-1 Rev response ele- ment (RRE) RNA and Ran. Found in a complex with HTLV-1 Rex, RANBP3 and Ran. Interacts with DDX3X, NUP88, NUP214, HIV-1 Rev, HTLV-1 Rex and RANBP3. Subcellular location: Nuclear and cytoplasmic. Located in the nucleoplasm, Cajal bodies and nucleoli. Shuttles between the nucleus/nucleolus and the cytoplasm. Tissue specificity: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. Not expressed in the kidney. Fig. 1. Residues 707-866 in 1w9cA colored by their relative importance. (See Miscellaneous: Cellular target of leptomycin B (LMB), a Appendix, Fig.7, for the coloring scheme.) XPO1/CRM1 nuclear export inhibitor. Similarity: Belongs to the exportin family. Similarity: Contains 10 HEAT repeats. Similarity: Contains 1 importin N-terminal domain. About: This Swiss-Prot entry is copyright. It is produced through a collaboration between the Swiss Institute of Bioinformatics and the EMBL outstation - the European Bioinformatics Institute. There are no restrictions on its use as long as its content is in no way modified and this statement is not removed. 2.2 Multiple sequence alignment for 1w9cA Fig. 2. Residues 867-1027 in 1w9cA colored by their relative importance. For the chain 1w9cA, the alignment 1w9cA.msf (attached) with 71 (See Appendix, Fig.7, for the coloring scheme.) sequences was used. The alignment was downloaded from the HSSP database, and fragments shorter than 75% of the query as well as duplicate sequences were removed. It can be found in the attachment 2.4 Top ranking residues in 1w9cA and their position on to this report, under the name of 1w9cA.msf. Its statistics, from the the structure alistat program are the following: In the following we consider residues ranking among top 25% of residues in the protein . Figure 3 shows residues in 1w9cA colored Format: MSF by their importance: bright red and yellow indicate more conser- Number of sequences: 71 ved/important residues (see Appendix for the coloring scheme). A Total number of residues: 22519 Pymol script for producing this figure can be found in the attachment. Smallest: 281 Largest: 321 Average length: 317.2 2.4.1 Clustering of residues at 25% coverage. Fig. 4 shows the Alignment length: 321 top 25% of all residues, this time colored according to clusters they Average identity: 43% belong to. The clusters in Fig.4 are composed of the residues listed Most related pair: 98% in Table 1. Most unrelated pair: 19% Table 1. Most distant seq: 34% cluster size member color residues red 75 716,717,721,725,728,732,736 Furthermore, 2% of residues show as conserved in this alignment. 748,749,751,752,754,756,758 The alignment consists of 36% eukaryotic ( 4% vertebrata, 2% 784,785,787,788,795,796,797 arthropoda, 18% fungi, 1% plantae) sequences. (Descriptions of 798,799,800,801,822,823,827 some sequences were not readily available.) The file containing the 830,831,833,834,842,844,845 sequence descriptions can be found in the attachment, under the name 848,849,851,852,855,859,860 1w9cA.descr. 862,863,866,880,881,883,884 885,887,889,890,893,894,903 929,931,932,934,935,936,938 2.3 Residue ranking in 1w9cA 939,942,945,946,982,986,997 The 1w9cA sequence is shown in Figs. 1–2, with each residue colo- 1011,1016,1017,1018,1019 red according to its estimated importance. The full listing of residues continued in next column in 1w9cA can be found in the file called 1w9cA.ranks sorted in the attachment. 2 2.4.2 Overlap with known functional surfaces at 25% coverage. The name of the ligand is composed of the source PDB identifier and the heteroatom name used in that file. Interface with 1w9cB.Table 2 lists the top 25% of residues at the interface with 1w9cB. The following table (Table 3) suggests possible disruptive replacements for these residues (see Section 3.6). Table 2. res type subst’s cvg noc/ dist (%) bb (A˚ ) 709 Q Q(90) 0.07 15/13 3.19 E(5) I(1) .(2) 758 L L(85) 0.10 34/3 3.63 I(5) M(7) F(1) 754 E E(92) 0.12 45/7 2.61 D(2) S(1) N(1) Fig. 3. Residues in 1w9cA, colored by their relative importance. Clockwise: V(1) front, back, top and bottom views. 717 M V(4) 0.18 8/2 3.96 L(12) M(78) F(2) I(1) 748 M L(64) 0.21 11/5 3.62 M(29) V(4) Q(1) 751 V V(42) 0.21 16/4 3.54 I(46) M(2) A(5) S(2) 716 D D(84) 0.24 36/12 2.90 E(1) G(2) P(1) H(1) .(2) N(5) Table 2. The top 25% of residues in 1w9cA at the interface with 1w9cB. (Field names: res: residue number in the PDB entry; type: amino acid type; substs: substitutions seen in the alignment; with the percentage of each type Fig. 4. Residues in 1w9cA, colored according to the cluster they belong to: in the bracket; noc/bb: number of contacts with the ligand, with the number of red, followed by blue and yellow are the largest clusters (see Appendix for contacts realized through backbone atoms given in the bracket; dist: distance the coloring scheme). Clockwise: front, back, top and bottom views. The of closest apporach to the ligand. ) corresponding Pymol script is attached. Table 3. res type disruptive Table 1. continued mutations cluster size member 709 Q (Y)(H)(FTW)(CG) color residues continued in next column Table 1. Clusters of top ranking residues in 1w9cA. 3 Table 3. continued res type disruptive mutations 758 L (YR)(T)(H)(SKECG) 754 E (H)(FW)(R)(Y) 717 M (Y)(T)(HR)(SCG) 748 M (Y)(H)(T)(R) 751 V (YR)(K)(E)(H) 716 D (R)(FWH)(Y)(VCAG) Table 3. List of disruptive mutations for the top 25% of residues in 1w9cA, that are at the interface with 1w9cB. Fig. 6. A possible active surface on the chain 1w9cA. The larger cluster it belongs to is shown in blue. Table 4. continued res type substitutions(%) cvg 845 R R(100) 0.02 880 W W(100) 0.02 884 H H(100) 0.02 894 L L(100) 0.02 788 Y Y(98)F(1) 0.03 860 F F(98)I(1) 0.03 736 G G(97)N(1)T(1) 0.04 844 H H(94)F(5) 0.04 848 F F(94)L(5) 0.04 935 H H(98)K(1) 0.04 787 D D(98)V(1) 0.05 827 F F(97)L(2) 0.06 752 K K(95)R(4) 0.07 800 V V(91)A(5)L(1) 0.07 I(1) 931 T T(91)C(2)M(5) 0.07 796 R R(87)K(12) 0.08 851 L L(92)F(5)M(1) 0.08 833 M M(95)I(4) 0.09 929 V V(88)T(2)A(7) 0.09 Fig.
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