title: Conformational analysis of processivity clamps in solution demonstrates that tertiary structure does not correlate with protein dynamics.
abstract: The relationship between protein sequence, structure, and dynamics has been elusive. Here, we report a comprehensive analysis using an in-solution experimental approach to study how the conservation of tertiary structure correlates with protein dynamics. Hydrogen exchange measurements of eight processivity clamp proteins from different species revealed that, despite highly similar three-dimensional structures, clamp proteins display a wide range of dynamic behavior. Differences were apparent both for structurally similar domains within proteins and for corresponding domains of different proteins. Several of the clamps contained regions that underwent local unfolding with different half-lives. We also observed a conserved pattern of alternating dynamics of the α helices lining the inner pore of the clamps as well as a correlation between dynamics and the number of salt bridges in these α helices. Our observations reveal that tertiary structure and dynamics are not directly correlated and that primary structure plays an important role in dynamics.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Nevin
authors.affiliation: Institute of Biotechnology, Vilnius University, LT-02241 Vilnius, Lithuania.
authors.forename: Visvaldas
authors.initials: V
authors.lastname: Kairys
authors.affiliation: Institute of Biotechnology, Vilnius University, LT-02241 Vilnius, Lithuania.
authors.forename: Česlovas
authors.initials: Č
authors.lastname: Venclovas
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Engen
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: Penny J
authors.initials: PJ
authors.lastname: Beuning
mesh_terms: D017360:Arabidopsis / Q000737:chemistry / Q000201:enzymology; D017122:Bacteriophage T4 / Q000737:chemistry / Q000201:enzymology; D004258:DNA Polymerase III / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D015870:Gene Expression; D006207:Half-Life; D006801:Humans; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology; D013045:Species Specificity; D040681:Structural Homology, Protein; D019712:Thermococcus / Q000737:chemistry / Q000201:enzymology
chemical_list: D011994:Recombinant Proteins; D004258:DNA Polymerase III