Tandem-repeat proteins conformational mechanics are optimized to facilitate functional interactions and complexations.

ABSTRACT

The architectures of tandem-repeat proteins are distinct from those of globular proteins. Individual modules, each comprising small structural motifs of 20-40 residues, are arrayed in a quasi one-dimensional fashion to form striking, elongated, horseshoe-like, and superhelical architectures, stabilized solely by short-range interaction. The spring-like shapes of repeat arrays point to elastic modes of action, and these proteins function as adapter molecules or 'hubs,' propagating signals within multi-subunit assemblies in diverse biological contexts. This flexibility is apparent in the dramatic variability observed in the structures of tandem-repeat proteins in different complexes. Here, using computational analysis, we demonstrate the striking ability of just one or a few global motions to recapitulate these structures. These findings show how the mechanics of repeat arrays are robustly enabled by their unique architecture. Thus, the repeating architecture has been optimized by evolution to favor functional modes of motions. The global motions enabling functional transitions can be fully visualized at http//bahargroup.org/tr_web.