2azs: Difference between revisions
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'''NMR structure of the N-terminal SH3 domain of Drk (calculated without NOE restraints)''' | '''NMR structure of the N-terminal SH3 domain of Drk (calculated without NOE restraints)''' | ||
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[[Category: Singer, A U.]] | [[Category: Singer, A U.]] | ||
[[Category: Tollinger, M.]] | [[Category: Tollinger, M.]] | ||
[[Category: | [[Category: Drk]] | ||
[[Category: | [[Category: Drosophila melanogaster]] | ||
[[Category: | [[Category: Nmr structure]] | ||
[[Category: | [[Category: Sh3 fragment]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:40:23 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 19:40, 3 May 2008
NMR structure of the N-terminal SH3 domain of Drk (calculated without NOE restraints)
OverviewOverview
The N-terminal SH3 domain of the Drosophila adapter protein Drk (drkN SH3 domain) is marginally stable (DeltaG(U) = 1 kcal/mol) and exists in equilibrium between folded and highly populated unfolded states. The single substitution T22G, however, completely stabilizes the protein (DeltaG(U) = 4.0 kcal/mol). To probe the causes of instability of the wild-type (WT) protein and the dramatic stabilization of the mutant, we determined and compared nuclear magnetic resonance structures of the folded WT and mutant drkN SH3 domains. Residual dipolar coupling (RDC) and carbonyl chemical-shift anisotropy (C'-CSA) restraints measured for the WT and T22G domains were used for calculating the structures. The structures for the WT and mutant are highly similar. Thr22 of the WT and Gly22 of the mutant are at the i + 2 position of the diverging, type-II beta-turn. Interestingly, not only Gly22 but also Thr22 successfully adopt an alpha(L) conformation, required at this position of the turn, despite the fact that positive phi values are energetically unfavorable and normally disallowed for threonine residues. Forcing the Thr22 residue into this unnatural conformation increases the free energy of the folded state of the WT domain relative to its T22G mutant. Evidence for residual helix formation in the diverging turn region has been previously reported for the unfolded state of the WT drkN SH3 domain, and this, in addition to other residual structure, has been proposed to play a role in decreasing the free energy of the unfolded state of the protein. Together these data provide evidence that both increasing the free energy of the folded state and decreasing the free energy of the unfolded state of the protein contribute to instability of the WT drkN SH3 domain.
About this StructureAbout this Structure
2AZS is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
ReferenceReference
Structural comparison of the unstable drkN SH3 domain and a stable mutant., Bezsonova I, Singer A, Choy WY, Tollinger M, Forman-Kay JD, Biochemistry. 2005 Nov 29;44(47):15550-60. PMID:16300404 Page seeded by OCA on Sat May 3 19:40:23 2008