TY - JOUR T1 - Changes in Dynamics upon Oligomerization Regulate Substrate Binding and Allostery in Amino Acid Kinase Family Members A1 - Marcos, Enrique A1 - Crehuet, Ramon A1 - Bahar, Ivet Y1 - 2011/09/29 N2 - Author Summary Protein function requires a three-dimensional structure with specific dynamic features for catalytic and binding events, and, in many cases, the structure results from the assembly of more than one polypeptide chain (also called monomer or subunit) to form an oligomer or multimer. Proteins such as hemoglobin or chaperonin GroEL are oligomers formed by 2 and 14 subunits, respectively, whereas virus capsids are multimers composed of hundreds of monomers. In these cases, the architecture of the interface between the subunits and the overall assembly geometry are essential in determining the functional motions that these sophisticated structures are able to perform under physiological conditions. Here we present results from our computational study of the large-amplitude motions of dimeric and hexameric proteins that belong to the Amino Acid Kinase family. Our study reveals that the monomers in these oligomeric proteins are arranged in such a way that the oligomer inherits the intrinsic dynamic features of its components. The packing geometry additionally confers the ability to perform highly cooperative conformational changes that involve all monomers and enable the biological activity of the multimer. The study highlights the significance of the quaternary design in favoring the oligomer dynamics that enables ligand-binding and allosteric regulation functions. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 7 IS - 9 UR - https://doi.org/10.1371/journal.pcbi.1002201 SP - e1002201 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002201 ER -