Evolution of a Protein Interaction Domain Family by Tuning Conformational Flexibility. J Am Chem Soc 2016 Nov 23;138(46):15150-15156
Date
08/10/2016Pubmed ID
27502157Pubmed Central ID
PMC5661941DOI
10.1021/jacs.6b05954Scopus ID
2-s2.0-84999106958 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Conformational flexibility allows proteins to adopt multiple functionally important conformations but can also lead to nonfunctional structures. We analyzed the dynamic behavior of the enzyme guanylate kinase as it evolved into the GK protein interaction domain (GKPID) to investigate the role of flexibility in the evolution of new protein functions. We found that the ancestral enzyme is very flexible, allowing it to adopt open conformations that can bind nucleotide and closed ones that enable catalysis of phosphotransfer from ATP to GMP. Historical mutations that converted the GK from an enzyme to a protein interaction domain dramatically reduce flexibility, predominantly by inhibiting rotations of the protein backbone that are coupled to the global closing motion. Removing flexibility prevents adoption of conformations that cannot fit the protein partner in the binding site. Our results highlight the importance of mutations that optimize protein conformational flexibility with function during evolution.
Author List
Whitney DS, Volkman BF, Prehoda KEAuthor
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Guanylate KinasesMolecular Dynamics Simulation
Nuclear Magnetic Resonance, Biomolecular
Protein Conformation
Protein Interaction Domains and Motifs
