spacer Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the superantigen SEC3 Variant 3B2
Primary citation
Title Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation
Authors Sundberg, E.J.search; Andersen, P.S.search; Schlievert, P.M.search; Karjalainen, K.search; Mariuzza, R.A.search
Journal STRUCTUREsearch vol:11, pag:1151-1161 (2003), Identifiers: PubMed ID (12962633)search DOI (10.1016/S0969-2126(03)00187-4)
Abstract Due to a paucity of studies that synthesize structural, energetic, and functional analyses of a series of protein complexes representing distinct stages in an affinity maturation pathway, the biophysical basis for the molecular evolution of protein-protein interactions is poorly understood. Here, we combine crystal structures and binding-free energies of a series of variant superantigen (SAG)-major histocompatibility complex (MHC) class II complexes exhibiting increasingly higher affinity to reveal that this affinity maturation pathway is controlled largely by two biophysical factors: shape complementarity and buried hydrophobic surface. These factors, however, do not contribute equivalently to the affinity maturation of the interface, as the former dominates the early steps of the maturation process while the latter is responsible for improved binding in later steps. Functional assays reveal how affinity maturation of the SAG-MHC interface corresponds to T cell activation by SAGs.
MeSH terms Binding Sitessearch, Enterotoxinssearch, HLA-DR1 Antigensearch, Histocompatibility Antigens Class IIsearch, Hydrophobic and Hydrophilic Interactionssearch, Lymphocyte Activationsearch, Modelssearch, Molecularsearch, Protein Bindingsearch, Protein Structuresearch, Quaternarysearch, Protein Structuresearch, Tertiarysearch, Signal Transductionsearch, Superantigenssearch, T-Lymphocytessearch
Other entries described in this publication 1jwm, 1jws
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