Principles and characteristics of biological assemblies in experimentally determined protein structures

Abstract

More than half of all structures in the PDB are assemblies of two or more proteins, including both homooligomers and heterooligomers. Structural information on these assemblies comes from X-ray crystallography, NMR, and cryo-EM spectroscopy. The correct assembly in an X-ray structure is often ambiguous, and computational methods have been developed to identify the most likely biologically relevant assembly based on physical properties of assemblies and sequence conservation in interfaces. Taking advantage of the large number of structures now available, some of the most recent methods have relied on similarity of interfaces and assemblies across structures of homologous proteins..

Assessment of protein assembly prediction in CASP13

“…Out of 42 targets, 12 were heteromeric and 30 homomeric, double the proportion of heteromers as would be expected if drawn randomly from the PDB . Two of the heteromeric targets presented uneven stoichiometry ( H0953 with stoichiometry A3B1 and H1022 with A6B3), a rather unusual event in the PDB with only 10% occurrence among all known heteromers …”

PDB-wide identification of physiological hetero-oligomeric assemblies based on conserved quaternary structure geometry

“…While numerous methods and resources discriminate crystal interfaces from physiologically relevant interfaces, as recently reviewed ( Capitani et al., 2016 ; Dey and Levy, 2018 ; Elez et al., 2020 ; Xu and Dunbrack, 2019 ), it is noteworthy that only a few methods make predictions on the whole protein assembly. PQS first addressed this challenge ( Henrick and Thornton, 1998 ), and currently, the primary such resources are PISA ( Krissinel and Henrick, 2007 ), EPPIC ( Bliven et al., 2018 ), and QSalign ( Dey et al., 2018 ).…”

Generating a High Valency Biotin Binder by Selecting Uniform Protein Assemblies via Crystallization

“…All dimeric avidins published to date demonstrate a higher oligomeric assembly in the crystalline states than initially analyzed in solution. Interfaces conserved between similar proteins are often indicative of biological relevance [42], thus the reoccurrence of this phenomenon led to re-examination of the solution state of hoefavidin and facilitated the construction of the covalently stabilized hoefavidin octamer. The dissolved crystals of P61C hoefavidin display the octameric cylindrical structure via transmission electron microscope (TEM).…”