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Dynamics of Proteins in Solution Biophysics

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Dynamics of Proteins in Solution Biophysics Quarterly Reviews of Dynamics of proteins in solution Biophysics Marco Grimaldo1,2, Felix Roosen-Runge1,3, Fajun Zhang2, Frank Schreiber2 cambridge.org/qrb and Tilo Seydel1 1Institut Max von Laue - Paul Langevin, 71 avenue des Martyrs, 38042 Grenoble, France; 2Institut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany and 3Division for Physical Review Chemistry, Lund University, Naturvetarvägen 14, 22100 Lund, Sweden Cite this article: Grimaldo M, Roosen-Runge F, Abstract Zhang F, Schreiber F, Seydel T (2019). Dynamics of proteins in solution. Quarterly The dynamics of proteins in solution includes a variety of processes, such as backbone and Reviews of Biophysics 52, e7, 1–63. https:// side-chain fluctuations, interdomain motions, as well as global rotational and translational doi.org/10.1017/S0033583519000027 (i.e. center of mass) diffusion. Since protein dynamics is related to protein function and essen- tial transport processes, a detailed mechanistic understanding and monitoring of protein Received: 15 February 2019 Revised: 27 February 2019 dynamics in solution is highly desirable. The hierarchical character of protein dynamics Accepted: 4 March 2019 requires experimental tools addressing a broad range of time- and length scales. We discuss how different techniques contribute to a comprehensive picture of protein dynamics, and Key words: focus in particular on results from neutron spectroscopy. We outline the underlying principles Quasielastic neutron spectroscopy; protein diffusion; protein backbone; protein side and review available instrumentation as well as related analysis frameworks. chains; molecular relaxations; colloid physics Author for correspondence: Felix Roosen-Runge, E-mail: felix.roosen- Table of contents [email protected]; Tilo Seydel, E-mail: [email protected] Introduction 3 Importance of protein dynamics in the biological environment 3 Scope and outline of this review 3 Protein dynamics on hierarchical time- and length-scales 3 Overview: techniques addressing protein dynamics 5 Principles of neutron spectroscopy 9 Quasi-elastic neutron scattering theory 9 Relevance of QENS for protein dynamics 12 Experimental techniques 12 Modeling and analysis 16 Results 21 Dynamics of hydrated protein powders 24 General features of the dynamics of proteins in solution as seen by neutron scattering 27 From powder to solution: influence of solution conditions on protein dynamics 27 The dynamical transition in solution 29 Comparison of internal protein dynamics in native, molten and denatured states 30 Relations of protein dynamics to structure: from globular to intrinsically disordered proteins 34 Internal dynamics of proteins at high pressure 36 Adaptation of proteins to ambient and extreme temperatures 37 Collective internal motions in proteins 39 Combination of neutron spectroscopy techniques: alcohol dehydrogenase 41 In vivo neutron spectroscopy 41 © The Author(s) 2019. This is an Open Access In vitro studies on the effect of macromolecular crowding on protein dynamics 43 article, distributed under the terms of the Creative Commons Attribution- Dynamics of protein clusters, aggregates and glasses 47 NonCommercial-NoDerivatives licence (http:// creativecommons.org/licenses/by-nc-nd/4.0/), Concluding remarks 49 which permits non-commercial re-use, distribution, and reproduction in any medium, Summary 49 provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained List of symbols for commercial re-use or in order to create a derivative work. 〈Δr2〉 mean-squared displacement (MSD) 〈u2〉 apparent mean-squared displacement 2θ scattering angle b, bi scattering length coh coh coh bi , ba , bb coherent scattering length Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.234, on 26 Sep 2021 at 19:26:38, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0033583519000027 2 Marco Grimaldo et al. αβ binc, binc incoherent scattering length S (q, ω) coherent scattering function i a α β stretching factor in a stretched exponential S (q, ω) incoherent scattering function σ cp protein concentration s scattering cross-section σ cs salt concentration coh coherent scattering cross-section σ D, D(t) diffusion coefficient inc incoherent scattering cross-section D diffusion tensor t time D0 dilute limit diffusion coefficient T temperature Ds short-time diffusion coefficient T0 dynamical transition temperature (s) D self-diffusion coefficient Td denaturation temperature (s) Ds short-time self-diffusion coefficient Tm melting temperature (c) τ Ds short-time collective diffusion coefficient residence time or relaxation time (depending on (c) Dapp apparent collective diffusion coefficient model) (c) τ ballistic timescale D collective translational diffusion coefficient B t τ diffusive timescale D translational diffusion coefficient D t τ interaction timescale D rotational diffusion coefficient I r Θ incidence angle E energy v velocity E kinetic energy kin V protein volume E analyzer energy p 0 W(t) mean-squared displacement E neutron energy after scattering by the sample f ξ correlation length E neutron energy before scattering by the sample i Y (Ω) spherical harmonic functions w volume fraction lm G(r, t) van Hove correlation function Gs(r, t) van Hove self-correlation function γ, γ(q) global tumbling relaxation rate List of abbreviations aIF6, initiation factor 6 from Methanoc- Γ, Γ(q) internal relaxation rate aldococcus jannaschii; ADH, alcohol dehydrogenase; AFM, at- H(q) hydrodynamic function omic force microscopy; αSN, α-synuclein; BLA, bovine − h v energy transfer α-lactalbumin; BLG, bovine beta-lactoglobulin; BSA, bovine I(q, t) autocorrelation function (intermediate scattering serum albumin; CD, circular dichroism; CG, coarse grained; function) CI2, chymotrypsin inhibitor 2; CYP101, cytochrome P450cam; Ir(q, t) rotational autocorrelation function deoxyHb, deoxyhemoglobin; DLS, dynamic light scattering; It(q, t) translational autocorrelation function eIF6, initiation factor 6 from Saccharomyces cerevisiae;EINS, ω I(q, ), Is scattering intensity elastic incoherent neutron scattering; EISF, elastic incoherent Ia absorbed intensity structure factor; EPR, electron paramagnetic resonance; FCS, jl(.) spherical Bessel function of first kind and l-th fluorescence correlation spectroscopy; FRAP, fluorescence order recovery after photobleaching; FRET, Föster resonance energy k, k wavevector and its magnitude transfer; GFP, green fluorescent protein; Hb, hemoglobin; ki, ki neutron wavevector before scattering and its HbCO, carbonmonoxyhemoglobin; HDX, exchange-mass spec- magnitude trometry; hIgG, human immunoglobulin G; HWHM, half kf , kf neutron wavevector after scattering and its width at half maximum; IDP, intrinsically disordered protein; magnitude IF6, initiation factor 6; IgG, immunoglobulin G; IHP, inositol L length scale hexaphosphate; IR, infrared; Ip, ‘intermediate’ pepsin (partially λ wavelength unfolded at pH 8); IRO, intermediate range order; K247R-Tn- L(.) Lorentzian function CD, troponin core domain, mutant TnT2; Lys, lysozyme; LOV, m mass light, oxygen, voltage; MalDH, malate dehydrogenase; MBLA, N total number of particles molten globule bovine α-lactalbumin; NBS, neutron backscatter- Ω solid angle ing; NMR, nuclear magnetic resonance; N-LDL, normolipidemic Ωα orientation of individual atoms low-density lipoprotein; Np, native pepsin; NpP, pepstatin-bound p fraction of atoms immobile on the accessible native pepsin; NSE, neutron spin-echo; PAN, proteasome-activating timescale nucleotidase; PFG-NMR, pulsed-field gradient nuclear magnetic q scattering vector (momentum transfer) resonance; PGK, phosphoglycerate kinase; PGKsub, substrate- r position bound phosphoglycerate kinase; pIgG, pig immunoglobulin G; R radius of atomic confinement ProTα, prothymosin α; PST, phase-space transformer; PVP, Ria, Rib position of particle i and type α or β poly(vinylpyrrolidone); QENS, quasielastic neutron scattering; Reff effective protein radius RBC, red blood cell; Rp, refolded; rOPN, recombinant osteopontin; Rh hydrodynamic radius SANS, small angle neutron scattering; SAXS, small angle X-ray scat- Rp protein radius tering; snase, staphylococcal nuclease; TG-LDL, triglyceride-rich ρ(r) radial distribution function low-density lipoprotein; TMAO, trimethylamine-N-oxide; TOF, r(r, t) microscopic particle density operator time-of-flight; TRXS, time resolved X-ray solution scattering; S(q) structure factor wtTn-CD, wild type troponin core domain; XPCS, X-ray photon S(q, ω) scattering function correlation spectroscopy. Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.234, on 26 Sep 2021 at 19:26:38, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0033583519000027 Quarterly Reviews of Biophysics 3 Introduction ultimately better understand intracellular processes of life such as biomolecular self-assembly and dynamical function of enzymes. Importance of protein dynamics in the biological environment Proteins are considered the machinery of life. They are an exciting subject of study for many branches of modern science and tech- Scope and outline of this review nology, from biology to medicine and pharmacy, but also in col- The current review aims for a systematic and organized overview on loid science, chemical engineering and nanotechnology. protein dynamics
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