Mathiharan, Yamuna Kalyani and Pappachan, Anju and Savithri, HS and Murthy, Mathur RN (2013) Dramatic Structural Changes Resulting from the Loss of a Crucial Hydrogen Bond in the Hinge Region Involved in C-Terminal Helix Swapping in SurE: A Survival Protein from Salmonella typhimurium. In: PLOS ONE, 8 (2).
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Abstract
Domain swapping is an interesting feature of some oligomeric proteins in which each protomer of the oligomer provides an identical surface for exclusive interaction with a segment or domain belonging to another protomer. Here we report results of mutagenesis experiments on the structure of C-terminal helix swapped dimer of a stationary phase survival protein from Salmonella typhimurium (StSurE). Wild type StSurE is a dimer in which a large helical segment at the C-terminus and a tetramerization loop comprising two beta strands are swapped between the protomers. Key residues in StSurE that might promote C-terminal helix swapping were identified by sequence and structural comparisons. Three mutants in which the helix swapping is likely to be avoided were constructed and expressed in E. coli. Three-dimensional X-ray crystal structures of the mutants H234A and D230A/H234A could be determined at 2.1 angstrom and 2.35 angstrom resolutions, respectively. Contrary to expectations, helix swapping was mostly retained in both the mutants. The loss of the crucial D230 OD2- H234 NE2 hydrogen bond (2.89 angstrom in the wild type structure) in the hinge region was compensated by new inter and intra-chain interactions. However, the two fold molecular symmetry was lost and there were large conformational changes throughout the polypeptide. In spite of these changes, the dimeric structure and an approximate tetrameric organization were retained, probably due to the interactions involving the tetramerization loop. Mutants were mostly functionally inactive, highlighting the importance of precise inter-subunit interactions for the symmetry and function of StSurE.
| Item Type: | Journal Article |
|---|---|
| Publication: | PLOS ONE |
| Publisher: | PUBLIC LIBRARY SCIENCE |
| Additional Information: | Copyright for this article belongs to PUBLIC LIBRARY SCIENCE, USA |
| Department/Centre: | Division of Biological Sciences > Biochemistry Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 25 Mar 2013 10:22 |
| Last Modified: | 25 Mar 2013 10:22 |
| URI: | http://eprints.iisc.ac.in/id/eprint/46168 |
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