Cooperative interactions and a non-native buried Trp in the unfolded state of an SH3 domain.


Abstract

The presence of residual structure in the unfolded state of the N-terminal SH3 domain of Drosophila drk (drkN SH3 domain) has been investigated using far- and near-UV circular dichroism (CD), fluorescence, and NMR spectroscopy. The unfolded (U(exch)) state of the drkN SH3 domain is significantly populated and exists in equilibrium with the folded (F(exch)) state under non-denaturing conditions near physiological pH. Denaturation experiments have been performed on the drkN SH3 domain in order to monitor the change in ellipticity, fluorescence intensity, and chemical shift between the U(exch) state and chemically or thermally denatured states. Differences between the unfolded and chemically or thermally denatured states highlight specific areas of residual structure in the unfolded state that are cooperatively disrupted upon denaturation. Results provide evidence for cooperative interactions in the unfolded state involving residues of the central beta-sheet, particularly the beta4 strand. Denaturation as well as hydrogen-exchange experiments demonstrate a non-native burial of the Trp ring within this "cooperative" core of the unfolded state. These findings support the presence of non-native hydrophobic clusters, organised by Trp rings, within disordered states. Study holds ProTherm entries: 15694, 15695, 15696, 15697 Extra Details: N-terminal SH3 domain unfolded state; SH3 domain; cooperativity; residual structure; NMR

Submission Details

ID: jDFwhyxR

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:46 p.m.

Version: 1

Publication Details
Crowhurst KA;Tollinger M;Forman-Kay JD,J. Mol. Biol. (2002) Cooperative interactions and a non-native buried Trp in the unfolded state of an SH3 domain. PMID:12215422
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
2AZS 2005-12-13 NMR structure of the N-terminal SH3 domain of Drk (calculated without NOE restraints)
2A36 2005-12-13 Solution structure of the N-terminal SH3 domain of DRK
2AZV 2005-12-13 Solution structure of the T22G mutant of N-terminal SH3 domain of DRK (calculated without NOEs)
2A37 2005-12-13 Solution structure of the T22G mutant of N-terminal SH3 domain of DRK (DRKN SH3 DOMAIN)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Protein enhancer of sevenless 2B Q6YKA8 DRK_DROSI
100.0 Protein enhancer of sevenless 2B Q08012 DRK_DROME