Parallel dynamics and evolution: Protein conformational fluctuations and assembly reflect evolutionary changes in sequence and structure

Abstract

Protein structure is dynamic: the intrinsic flexibility of polypeptides facilitates a range of conformational fluctuations, and individual protein chains can assemble into complexes. Proteins are also dynamic in evolution: significant variations in secondary, tertiary and quaternary structure can be observed among divergent members of a protein family. Recent work has highlighted intriguing similarities between these structural and evolutionary dynamics occurring at various levels. Here we review evidence showing how evolutionary changes in protein sequence and structure are often closely related to local protein flexibility and disorder, large-scale motions and quaternary structure assembly. We suggest that these correspondences can be largely explained by neutral evolution, while deviations between structural and evolutionary dynamics can provide valuable functional insights. Finally, we address future prospects for the field and practical applications that arise from a deeper understanding of the intimate relationship between protein structure, dynamics, function and evolution.

Biophysics of protein evolution and evolutionary protein biophysics

“…For proteins that have both ordered and disordered regions, mutations in IDRs lead to smaller stability changes than in ordered regions. Thus, IDPs/IDRs may enhance protein evolvability and the development of new functions [242], as evolutionary changes in protein sequence and structure are often correlated with local flexibility and disorder [243].…”

Protein Flexibility Facilitates Quaternary Structure Assembly and Evolution

“…If there existed a tendency for more flexible proteins to evolve at a faster rate, then more flexible proteins might simply appear to be more recent due to their lower conservation. Generally it is thought that, although the more flexible regions of a given protein tend to evolve more quickly than its more rigid regions, there is little correspondence between flexibility and evolutionary conservation at the global protein level [17]. We address this further in Figure S6, showing that there is no clear propensity for evolutionarily newer proteins to be more flexible overall (i.e., when not considered at the individual complex level), although there is a slight tendency for the most highly flexible proteins to be less conserved.…”

“…How does flexibility facilitate the assembly of multiple proteins into a protein complex? And given that quaternary structures can evolve in a process analogous to assembly [12],[13],[17], has flexibility been important for this evolution?…”

Predicting Evolutionary Site Variability from Structure in Viral Proteins: Buriedness, Packing, Flexibility, and Design

“…Patterns of amino-acid sequence variation in protein-coding genes are shaped by the structure and function of the expressed proteins (Wilke and Drummond 2010; Liberles et al 2012; Marsh and Teichmann 2014). As the most basic reflection of this relationship, buried residues in proteins tend to be more evolutionarily conserved than exposed residues (Overington et al 1992; Goldman et al 1998; Mirny and Shakhnovich 1999; Dean et al 2002).…”