Regulation of multimerization by terminal protein tails: The avidin family

The avidin – biotin system has been utilized for decades, exploiting the high affinity binding as specific molecular glue in various and diverse biotechnological applications, with tetrameric avidin, and its bacterial analog streptavidin widely used. Attempts to expand the biotin based toolbox led to the discovery of a new sub-family of avidins comprised of two monomers, thus termed dimeric avidins. Further investigation into the multimeric assembly of dimeric avidins reveals an intriguing phenomenon: Many dimeric avidins form higher oligomeric assemblies in the crystal structure, either hexamers or octamers. This finding was initially regarded as a crystallization fluke, and servers such as EPPIC and PISA did not predict biological relevance as well. Importantly, examination of several dimeric avidins using experimental methods such as IEX-MALS (Ion Exchange coupled to Multi Angle Light Scattering) identified multimers even in solution. We are studying and solving more structures of dimeric avidins, in order to shed light on this discovery, and to reveal conserved characteristics of these interactions. The assemblies studied here are mostly stabilized by C-terminal regions, which interact with the biotin-binding site of neighboring monomers and contribute greatly to the oligomeric formation. This raises the possibility of a general phenomenon of tail-mediated multimerization and regulation. Thus, we have extended our analysis to additional occurrences of terminal regions interacting with neighboring monomers within a determined crystal structure, and investigate their potential biological relevance.