title: Dehydron: a structurally encoded signal for protein interaction.
abstract: We introduce a quantifiable structural motif, called dehydron, that is shown to be central to protein-protein interactions. A dehydron is a defectively packed backbone hydrogen bond suggesting preformed monomeric structure whose Coulomb energy is highly sensitive to binding-induced water exclusion. Such preformed hydrogen bonds are effectively adhesive, since water removal from their vicinity contributes to their stability. At the structural level, a significant correlation is established between dehydrons and sites for protein complexation, with the HIV-1 capsid protein P24 complexed with antibody light-chain FAB25.3 providing the most dramatic correlation. Furthermore, the number of dehydrons in homologous similar-fold proteins from different species is shown to be a signature of proteomic complexity. The techniques are then applied to higher levels of organization: The formation of the capsid and its organization in picornaviruses correlates strongly with the distribution of dehydrons on the rim of the virus unit. Furthermore, antibody contacts and crystal contacts may be assigned to dehydrons still prevalent after the capsid has been assembled. The implications of the dehydron as an encoded signal in proteomics, bioinformatics, and inhibitor drug design are emphasized.
authors.affiliation: Institute for Biophysical Dynamics, The University of Chicago, Illinois 60637, USA. ariel@uchicago.edu
authors.forename: Ariel
authors.initials: A
authors.lastname: Fernández
authors.forename: Ridgway
authors.initials: R
authors.lastname: Scott
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D036022:Capsid Proteins / Q000737:chemistry; D019992:Databases as Topic; D015195:Drug Design; D016655:HIV Core Protein p24 / Q000737:chemistry; D006860:Hydrogen Bonding; D007128:Immunoglobulin Fragments / Q000737:chemistry; D008574:Mengovirus / Q000378:metabolism; D008958:Models, Molecular; D008962:Models, Theoretical; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020543:Proteome; D012229:Rhinovirus / Q000378:metabolism; D012984:Software; D014867:Water / Q000737:chemistry
chemical_list: D036022:Capsid Proteins; D016655:HIV Core Protein p24; D007128:Immunoglobulin Fragments; D020543:Proteome; D014867:Water