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 \textit{in vivo }adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e. \textit{Borrelia burgdorferi }VlsE) under 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 \textit{in vivo}.