title: Energetics of oligomeric protein folding and association.
abstract: In nature, proteins most often exist as complexes, with many of these consisting of identical subunits. Understanding of the energetics governing the folding and misfolding of such homooligomeric proteins is central to understanding their function and misfunction, in disease or biotechnology. Much progress has been made in defining the mechanisms and thermodynamics of homooligomeric protein folding. In this review, we outline models as well as calorimetric and spectroscopic methods for characterizing oligomer folding, and describe extensive results obtained for diverse proteins, ranging from dimers to octamers and higher order aggregates. To our knowledge, this area has not been reviewed comprehensively in years, and the collective progress is impressive. The results provide evolutionary insights into the development of subunit interfaces, mechanisms of oligomer folding, and contributions of oligomerization to protein stability, function and regulation. Thermodynamic analyses have also proven valuable for understanding protein misfolding and aggregation mechanisms, suggesting new therapeutic avenues. Successful recent designs of novel, functional proteins demonstrate increased understanding of oligomer folding. Further rigorous analyses using multiple experimental and computational approaches are still required, however, to achieve consistent and accurate prediction of oligomer folding energetics. Modeling the energetics remains challenging but is a promising avenue for future advances.
authors.affiliation: Guelph-Waterloo Centre for Graduate Studies in Chemistry and Biochemistry, and Department of Chemistry, University of Waterloo, 200 University Ave. West, Waterloo, ON, Canada.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Doyle
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Rumfeldt
authors.forename: Helen R
authors.initials: HR
authors.lastname: Broom
authors.forename: Aron
authors.initials: A
authors.lastname: Broom
authors.forename: Peter B
authors.initials: PB
authors.lastname: Stathopulos
authors.forename: Kenrick A
authors.initials: KA
authors.lastname: Vassall
authors.forename: Johnathan J
authors.initials: JJ
authors.lastname: Almey
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Meiering
mesh_terms: D001704:Biopolymers / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods; D017510:Protein Folding; D013057:Spectrum Analysis / Q000379:methods; D013816:Thermodynamics
chemical_list: D001704:Biopolymers