Hsc70-interacting HPD loop of the J domain of polyomavirus T antigens fluctuates in ps to ns and micros to ms.
The backbone dynamics of the J domain from polyomavirus T antigens have been investigated using 15N NMR relaxation and molecular dynamics simulation. Model-free relaxation analysis revealed picosecond to nanosecond motions in the N terminus, the I-II loop, the C-terminal end of helix II through the HPD loop to the beginning of helix III, and the C-terminal end of helix III to the C terminus. The backbone dynamics of the HPD loop and termini are dominated by motions with moderately large amplitudes and correlation times of the order of a nanosecond or longer. Conformational exchange on the microsecond to millisecond timescale was identified in the HPD loop, the N and C termini, and the I-II loop. A 9.7ns MD trajectory manifested concerted swings of the HPD loop. Transitions between major and minor conformations of the HPD loop featured distinct patterns of change in backbone dihedral angles and hydrogen bonds. Fraying of the C-terminal end of helix II and the N-terminal end of helix III correlated with displacements of the HPD loop. Correlation of crankshaft motions of Gly46 and Gly47 with the collective motions of the HPD loop suggested an important role of the two glycine residues in the mobility of the loop. Fluctuations of the HPD loop correlated with relative reorientation of side-chains of Lys35 and Asp44 that interact with Hsc70.
Berjanskii
Mark
M
Department of Biochemistry, 117 Schweitzer Hall, University of Missouri, Columbia, MO 65211, USA.
Riley
Michael
M
Van Doren
Steven R
SR
D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D014461:Ultracentrifugation
D000952:Antigens, Polyomavirus Transforming; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins