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

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 proces

SUBMITTER: Cho S 

PROVIDER: S-EPMC2746401 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature