TY - JOUR

T1 - Anisotropic protein-protein interactions in dilute and concentrated solutions

AU - Pasquier, Coralie

AU - Midtgaard, Soren Roi

AU - Polimeni, Marco

AU - Jorgensen, Christian Isak

AU - Arleth, Lise

AU - Callisen, Thomas H.

AU - Lund, Mikael

PY - 2023/1

Y1 - 2023/1

N2 - Interactions between biomolecules are ubiquitous in nature and crucial to many applications including vaccine development; environmentally friendly textile detergents; and food formulation. Using small angle X-ray scattering and structure-based molecular simulations, we explore protein-protein interactions in dilute to semi-concentrated protein solutions. We address the pertinent question, whether interaction models developed at infinite dilution can be extrapolated to concentrated regimes? Our analysis is based on measured and simulated osmotic second virial coefficients and solution structure factors at varying protein concentration and for different variants of the protein Thermomyces Lanuginosus Lipase (TLL). We show that in order to span the dilute and semi-concentrated regime, any model must carefully capture the balance between spatial and orientational correlations as the protein concentration is elevated. This requires consideration of the protein surface morphology, including possible patch interactions. Experimental data for TLL is most accurately described when assuming a patchy interaction, leading to dimer formation. Our analysis supports that the dimeric proteins predominantly exist in their open conformation where the active site is exposed, thereby maximising hydrophobic attractions that promote inter-protein alignment.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

AB - Interactions between biomolecules are ubiquitous in nature and crucial to many applications including vaccine development; environmentally friendly textile detergents; and food formulation. Using small angle X-ray scattering and structure-based molecular simulations, we explore protein-protein interactions in dilute to semi-concentrated protein solutions. We address the pertinent question, whether interaction models developed at infinite dilution can be extrapolated to concentrated regimes? Our analysis is based on measured and simulated osmotic second virial coefficients and solution structure factors at varying protein concentration and for different variants of the protein Thermomyces Lanuginosus Lipase (TLL). We show that in order to span the dilute and semi-concentrated regime, any model must carefully capture the balance between spatial and orientational correlations as the protein concentration is elevated. This requires consideration of the protein surface morphology, including possible patch interactions. Experimental data for TLL is most accurately described when assuming a patchy interaction, leading to dimer formation. Our analysis supports that the dimeric proteins predominantly exist in their open conformation where the active site is exposed, thereby maximising hydrophobic attractions that promote inter-protein alignment.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

KW - Protein-protein interactions

KW - Solution stability

KW - Molecular modelling

KW - Directional interactions

KW - Small-Angle X-ray Scattering

KW - X-RAY-SCATTERING

KW - THERMOMYCES-LANUGINOSA LIPASE

KW - MONTE-CARLO SIMULATIONS

KW - INTERFACIAL ACTIVATION

KW - DYNAMICS

KW - ELECTROSTATICS

KW - GLYCOSYLATION

KW - SURFACES

KW - SYSTEMS

KW - PH

U2 - 10.1016/j.jcis.2022.08.054

DO - 10.1016/j.jcis.2022.08.054

M3 - Journal article

C2 - 36099847

VL - 629

SP - 794

EP - 804

JO - Journal of Colloid and Interface Science

JF - Journal of Colloid and Interface Science

SN - 0021-9797

ER -