Structural Basis of Affinity Maturation and Intramolecular Cooperativity in a Protein-Protein Interaction
| Autor: | Roy A. Mariuzza, Jianying Yang, Eric J. Sundberg, Melissa C. Kerzic, Rongjin Guan, Michele C. Kieke, Chittoor P. Swaminathan, David M. Kranz, Sangwoo Cho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Stereochemistry Protein Conformation Receptors Antigen T-Cell alpha-beta Cooperativity Crystal structure medicine.disease_cause Crystallography X-Ray Article Affinity maturation 03 medical and health sciences Enterotoxins Mice Protein structure Structural Biology Protein Interaction Mapping medicine Animals Receptor Molecular Biology 030304 developmental biology 0303 health sciences Mutation Chemistry 030302 biochemistry & molecular biology A protein Water Peptide Fragments Amino Acid Substitution Intramolecular force |
| Popis: | SummaryAlthough 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|