Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation

Eric J Sundberg; Peter S Andersen; Patrick M Schlievert; Klaus Karjalainen; Roy A Mariuzza

doi:10.1016/S0969-2126(03)00187-4

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Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation

Journal article

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Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation

Eric J Sundberg, Peter S Andersen, Patrick M Schlievert, Klaus Karjalainen and Roy A Mariuzza

Structure (London), Vol.11(9), pp.1151-1161

09/2003

DOI: 10.1016/S0969-2126(03)00187-4

PMID: 12962633

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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.

Signal Transduction

Protein Structure, Tertiary

Lymphocyte Activation

Models, Molecular

HLA-DR1 Antigen - metabolism

Histocompatibility Antigens Class II - chemistry

Superantigens - metabolism

Superantigens - chemistry

T-Lymphocytes - metabolism

T-Lymphocytes - chemistry

Protein Structure, Quaternary

Enterotoxins - metabolism

Hydrophobic and Hydrophilic Interactions

Protein Binding

Histocompatibility Antigens Class II - metabolism

Enterotoxins - chemistry

Binding Sites

HLA-DR1 Antigen - chemistry

Details

Title: Subtitle: Structural, energetic, and functional analysis of a protein-protein interface at distinct stages of affinity maturation
Creators: Eric J Sundberg - Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA. sundberg@umbi.umd.edu
Peter S Andersen
Patrick M Schlievert
Klaus Karjalainen
Roy A Mariuzza
Resource Type: Journal article
Publication Details: Structure (London), Vol.11(9), pp.1151-1161
Publisher: United States
DOI: 10.1016/S0969-2126(03)00187-4
PMID: 12962633
ISSN: 0969-2126
eISSN: 1878-4186
Grant note: AI36900 / NIAID NIH HHS AI49564 / NIAID NIH HHS
Language: English
Date published: 09/2003
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984002377202771

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