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 language | English (US) |
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Pages (from-to) | 1775-1787 |
Number of pages | 13 |
Journal | Structure |
Volume | 13 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2005 |
Externally published | Yes |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology