Crowded, cell-like environment induces shape changes in aspherical protein.
How the crowded environment inside cells affects the structures of proteins with aspherical shapes is a vital question because many proteins and protein-protein complexes in vivo adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e., Borrelia burgdorferi VlsE) in crowded, cell-like conditions. The results show that macromolecular crowding affects protein-folding dynamics as well as overall protein shape. In crowded milieus, distinct conformational changes in VlsE are accompanied by secondary structure alterations that lead to exposure of a hidden antigenic region. Our work demonstrates the malleability of "native" proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo.
Homouz
Dirar
D
Department of Physics, University of Houston, Houston, TX 77204, USA.
Perham
Michael
M
Samiotakis
Antonios
A
Cheung
Margaret S
MS
Wittung-Stafshede
Pernilla
P
D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D003198:Computer Simulation; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008074:Lipoproteins; C105546:VlsE protein, Borrelia burgdorferi