Structural Basis of Affinity Maturation and Intramolecular Cooperativity in a Protein-Protein Interaction

Journal Article · Sat Jan 01 04:00:00 EST 2005 · Structure

DOI:https://doi.org/10.1016/j.str.2005.08.015· OSTI ID:913858

Cho, S; Swaminathan, C; Yang, J; Kerzic, M; Guan, R; Kieke, M; Kranz, D; Mariuzza, R; Sundberg, E

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 913858
• Report Number(s): BNL--78426-2007-JA
• Journal Information: Structure, Journal Name: Structure Journal Issue: 12 Vol. 13
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
AFFINITY
CRYSTAL STRUCTURE
PROTEIN STRUCTURE
PROTEINS
national synchrotron light source