Relaxation study of the backbone dynamics of human profilin by two-dimensional 1H-15N NMR.
The dynamic properties of 111 backbone HN sites in uncomplexed human profilin, a protein of 139 residues, have been characterized by two-dimensional inverse-detected 1H-15N NMR spectroscopy. Heteronuclear (1H)-15N nuclear Overhauser effects and 15N longitudinal and transverse relaxation rates have been analyzed in terms of model-free spectral density functions and exchange contributions to transverse relaxation rates. Relatively high mobilities on the nanosecond time-scale are observed for Asp26 and Ser27, which form part of a loop connecting beta-strands A and B, and for Thr92 through Ala95, which are in a loop connecting beta-strands E and F. Significant exchange contributions, indicative of motions on the microsecond to millisecond time-scale, have been obtained for 30 residues. These include Leu77, Asp80 and Gly81 of a loop between beta-strands D and E, Ser84 and Met85 of beta-strand E, Gly121 of a loop connecting beta-strand G and the C-terminal helix, and Gln138, which is next to the C-terminal residue Tyr139. Some of the regions showing high flexibility in profilin are known to be involved in poly-L-proline binding.
Constantine
K L
KL
Department of Macromolecular NMR, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Friedrichs
M S
MS
Bell
A J
AJ
Lavoie
T B
TB
Mueller
L
L
Metzler
W J
WJ
D000595:Amino Acid Sequence; D003285:Contractile Proteins / Q000737:chemistry; D006801:Humans; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008433:Mathematics; D008840:Microfilament Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009587:Nitrogen Isotopes; D051304:Profilins; D017510:Protein Folding; D017433:Protein Structure, Secondary
D003285:Contractile Proteins; D008840:Microfilament Proteins; D009587:Nitrogen Isotopes; C495738:PFN1 protein, human; D051304:Profilins; D006859:Hydrogen