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PMID: 16338406 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction.

Structure (London, England : 1993) ·Vol. 13 ·No. 12 ·2005-12-00 ·Pages 1775-87

Cho S, Swaminathan CP, Yang J, Kerzic MC, Guan R, Kieke MC, Kranz DM, Mariuzza RA, Sundberg EJ

Abstract

Although protein-protein interactions are involved in nearly all cellular processes, general rules for describing affinity and selectivity in protein-protein complexes are lacking, primarily because correlations between changes in protein structure and binding energetics have not been well determined. Here, we establish the structural basis of affinity maturation for a protein-protein interaction system that we had previously characterized energetically. This model system exhibits a 1500-fold affinity increase. Also, its affinity maturation is restricted by negative intramolecular cooperativity. With three complex and six unliganded variant X-ray crystal structures, we provide molecular snapshots of protein interface remodeling events that span the breadth of the affinity maturation process and present a comprehensive structural view of affinity maturation. Correlating crystallographically observed structural changes with measured energetic changes reveals molecular bases for affinity maturation, intramolecular cooperativity, and context-dependent binding.

MeSH Terms
Amino Acid Substitution Animals Crystallography, X-Ray Enterotoxins/chemistry,genetics Mice Models, Molecular Mutation Peptide Fragments/chemistry,genetics Protein Conformation Protein Interaction Mapping Receptors, Antigen, T-Cell, alpha-beta/chemistry,genetics Water/chemistry
Chemicals
Enterotoxins Peptide Fragments Receptors, Antigen, T-Cell, alpha-beta T-cell receptor Vbeta 8.2 Water enterotoxin C, staphylococcal
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Cho Sangwoo
Center for Advanced Research in Biotechnology, W.M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.
Swaminathan Chittoor P
Yang Jianying
Kerzic Melissa C
Guan Rongjin
Kieke Michele C
Kranz David M
Mariuzza Roy A
Sundberg Eric J
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
0969-2126
DOI
10.1016/j.str.2005.08.015
Published
2005-12-00
Pages
1775-87
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC2746401
Subset
IM
Grants
NIAID NIH HHS · R01 AI049564 · United States
NIAID NIH HHS · R37 AI036900 · United States
NIAID NIH HHS · R37 AI036900-12 · United States
NIGMS NIH HHS · GM52801 · United States
NIAID NIH HHS · R21 AI055882 · United States
NIAID NIH HHS · AI064611 · United States
NIAID NIH HHS · R01 AI064611 · United States
NIGMS NIH HHS · R01 GM055767 · United States
NIGMS NIH HHS · R01 GM052801 · United States
NIAID NIH HHS · AI55882 · United States
NIGMS NIH HHS · GM55767 · United States
NIAID NIH HHS · AI49564 · United States
Databases
PDB
2APB, 2APF, 2APT, 2APV, 2APW, 2APX, 2AQ1, 2AQ2, 2AQ3
Corrections
CommentIn
PMID: 16338399
External Links
PubMed source DOI: 10.1016/j.str.2005.08.015 PMC Full Text View journal details
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