Linked Life Data

19351132

Source:http://linkedlifedata.com/resource/pubmed/id/19351132

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2009-4-22
pubmed:abstractText
Structural heterogeneity is thought to be inherent in many proteins and may be important for their folding and/or function. However, it is difficult to detect by conventional methods. Carbon-deuterium bonds are environmentally sensitive, nonperturbative probes of protein environments whose observation and characterization are facilitated by their unique stretching absorption frequency in an otherwise unobscured region of the IR spectrum. We demonstrate that deuterium atoms incorporated at C(alpha) backbone positions (C(alpha)-D bonds) are sensitive to the local backbone structure and thus may be used not only to detect structural heterogeneity but also to help characterize it structurally. Density functional theory calculations are used to predict that C(alpha)-D bonds of glycine are sensitive to their local structure, with the absorptions red-shifted for an extended beta-sheet relative to gamma- and alpha-helix-like turns. These predictions are confirmed using the N-terminal Src homology 3 (nSH3) domain from the human CrkII adaptor protein, whose function as a signaling domain may require structural heterogeneity. Four nSH3 variants were synthesized in which individual glycine residues were site-specifically modified with C(alpha)D(2) glycine residues. Not only were the C(alpha)-D bonds incorporated within the beta-sheet of nSH3 more red-shifted than those incorporated within loops, but the data also reveal that nSH3 populates at least two discrete beta-sheet core structures. Moreover, the data suggest that the folded core of nSH3 may be less ordered than previously believed and also that the unfolded state may be more ordered than previously thought, and both of these factors may influence the folding and function of these important signaling domains. The C-D-based IR technique should be generally useful in the characterization of structure and heterogeneity of both folded and unfolded states.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5726-7
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Direct observation of structural heterogeneity in a beta-sheet.
pubmed:affiliation
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.