Title | Structural and dynamic characterization of intrinsically disordered human securin by NMR spectroscopy. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Csizmok, V., I. C. Felli, P. Tompa, L. Banci, and I. Bertini |
Journal | J Am Chem Soc |
Volume | 130 |
Issue | 50 |
Pagination | 16873-9 |
Date Published | 2008 Dec 17 |
Type of Article | idp |
ISSN | 1520-5126 |
Keywords | Algorithms, Cell Cycle Proteins, Endopeptidases, Humans, Neoplasm Proteins, Nuclear Magnetic Resonance, Biomolecular |
Abstract | Understanding the molecular action of securin, the inhibitor of separase in mitosis, is of immense theoretical and biomedical importance. The residue-level structural description of an intrinsically disordered protein of this length (202 amino acids, containing 24 prolines), however, represents a particular challenge. Here we combined (1)H-detected and (13)C-detected protonless NMR experiments to achieve full assignment of securin's backbone amide resonances. Chemical shifts, (15)N relaxation rates (R(1), R(2), (1)H-(15)N NOEs), (1)H exchange rates with the solvent (CLEANEX-PM), and (1)H-(15)N residual dipolar couplings were determined along the entire length of the protein. This analysis showed that securin is not entirely disordered, but segregates into a largely disordered N-terminal half and a C-terminal half with transient segmental order, within which the segment D(150)-F(159) has a significant helical tendency and segments E(113)-S(127) and W(174)-L(178) also show a significant deviation from random-coil behavior. These results, in combination with bioinformatic and biochemical data on the securin/separase interaction, shed light on the inhibitory action of securin on separase. |
DOI | 10.1021/ja805510b |
Alternate Journal | J. Am. Chem. Soc. |
PubMed ID | 19053469 |
Grant List | ISRF 067595 / / Wellcome Trust / United Kingdom |
- Log in to post comments
- Google Scholar
- PubMed
- DOI