To understand the molecular links between protein chemical structures, internal dynamics, and biochemical functions, we focus on the questions: What is the connection between a protein's biological function and its structural dynamics (i.e. the flexibility of various structural elements within a protein’s three-dimensional structure)? How do atomic structures and internal dynamics modulate biochemical activity? What is the functional significance of evolutionary conservation of certain amino acid residues in protein families? Proteins of interest involve (1) crenarchaeal viral proteins from Sulfolobus spindle shaped viruses; (2) proteins involved in heme acquisition and Staphylococcus aureus pathogen growth and survival; (3) leaf senescence and nitrogen remobilization in plants; (4) protein dynamics studies of functionally altered mutants of the tryptophan repressor protein (TrpR).
The adjacent figure shows the 3D solution structure of the E73 protein from the hyperthermophilic crenarchaeal Sulfolobus Spindle Shaped Virus – Ragged Hills (SSV-RH) as determined by NMR.
L. Taubner, E. Bienkiewicz, V. Copié, and B. Caughey , "Structure of the flexible amino terminal domain of prion protein bound to a sulfated glycan." J. Mol. Biol. 2010, Vol. 395, p.475-490
A. Goel, B. P. Tripet, R.C. Tyler, L.D. Nebert, and V. Copié , "Backbone amide dynamics studies of apo-L75F-TrpR, a temperature-sensitive mutant of the tryptophan repressor protein (TrpR): comparison with the 15N relaxation profiles of wild-type and A77V mutant apo-TrpR repressors." Biochemistry, 2010, Vol. 49, pp 8006-8019.
N. G. Lintner, K.A. Frankel, S.E Tsutakawa, D.L. Alsbury, V. Copié, M.J. Young, J.A. Tainer, and C.M Lawrence, "Structural insight into the CRISPR/CAS system from SSO1445, a CRISPR associated Csa3 protein from Sulfolobus solfataricus." J. Mol. Biol., 2011, 405(4) pp 939-955
B. P. Tripet, A. Goel, and V. Copié , "Internal dynamics of the tryptophan repressor (TrpR) and two functionally distinct TrpR variants, L75F-TrpR and A77V-TrpR, in their L-Trp-bound forms." Biochemistry, 2011, Vol. 50 pp. 5140-5153
C.S Schlenker, A. Goel, B. Tripet, T. Willi, S. Menon, C.M. Lawrence, and V. Copié , "Structure and Dynamics of the E73 protein from the hyperthermophilic archeal virus SSV-RH: Identification of an extended RHH structural motif whose DNA-binding function suggests a role in gene transcription regulation." Biochemistry – Submitted (Sept 30 2011)
N. G. Lintner, M. Kerou, S.K. Brumfield, S. Graham, H. Liu, Naismith, J.H., M. Sdano, N. Peng, Q. She, V. Copié, M.J. Young, M.F. White, and C.M. Lawrence, "Structural and Functional Characterization of an Archaeal CASCADE complex for CRISPR-mediated viral defense." J. Biol. Chem., 2011, Vol 286 pp. 21643-21656
C. Schlenker, S. Menon, C.M. Lawrence, and V. Copié , "1H, 13C, 15N Backbone and Sidechain Resonance Assignments for E73 from Sulfolobus Spindle Shaped Virus Ragged Hills, a hyperthermophilic Crenarchaeal Virus from Yellowstone National Park.." J. Biomol. NMR Assignments, 2009, Vol. 3, pp. 219-222
Biochemistry, Biophysical, Chemical Biology, NMR, Protein Chemistry, Spectroscopy