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

Sangwoo Cho, Chittoor P. Swaminathan, Jianying Yang, Melissa C. Kerzic, Rongjin Guan, Michele C. Kieke, David M. Kranz, Roy A. Mariuzza, Eric J. Sundberg

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1775-1787
Number of pages13
JournalStructure
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2005

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Proteins
Molecular Structure
Protein Binding
X-Rays

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Cho, S., Swaminathan, C. P., Yang, J., Kerzic, M. C., Guan, R., Kieke, M. C., ... Sundberg, E. J. (2005). Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction. Structure, 13(12), 1775-1787. https://doi.org/10.1016/j.str.2005.08.015

Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction. / Cho, Sangwoo; Swaminathan, Chittoor P.; Yang, Jianying; Kerzic, Melissa C.; Guan, Rongjin; Kieke, Michele C.; Kranz, David M.; Mariuzza, Roy A.; Sundberg, Eric J.

In: Structure, Vol. 13, No. 12, 01.12.2005, p. 1775-1787.

Research output: Contribution to journalArticle

Cho, S, Swaminathan, CP, Yang, J, Kerzic, MC, Guan, R, Kieke, MC, Kranz, DM, Mariuzza, RA & Sundberg, EJ 2005, 'Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction', Structure, vol. 13, no. 12, pp. 1775-1787. https://doi.org/10.1016/j.str.2005.08.015
Cho, Sangwoo ; Swaminathan, Chittoor P. ; Yang, Jianying ; Kerzic, Melissa C. ; Guan, Rongjin ; Kieke, Michele C. ; Kranz, David M. ; Mariuzza, Roy A. ; Sundberg, Eric J. / Structural basis of affinity maturation and intramolecular cooperativity in a protein-protein interaction. In: Structure. 2005 ; Vol. 13, No. 12. pp. 1775-1787.
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