1ncu
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TITIN MODULE M5, N-TERMINALLY EXTENDED, NMR
OverviewOverview
In the course of a structural study of titin, a giant modular protein from, muscle, we have reported that N-terminal extension of immunoglobulin-like, (Ig-like) domains from titin stabilizes this fold. In order to investigate, the structural basis of such an effect, we have solved the structure of, NEXTM5, which has six amino acids added to the sequence of M5, a domain, for which full structure determination has been previously achieved. In, the present work, the structures and the dynamics of M5 and NEXTM5 are, compared in the light of data collected for these and other titin domains., In NEXTM5, three out of the six added residues are structured and pack, against the nearby BC and FG loops. As a consequence, three new backbone, hydrogen bonds are formed with the B strand, extending the A strand by two, residues and decreasing the exposed surface area of the loops. Additional, contacts which involve the side-chains give rise to a remarkable pH, dependence of the stability. Interestingly, no correlation is observed on, the NMR time-scale between the overall dynamics of the extended domain and, its increased stability. The most noticeable differences between the two, constructs are localised around the N terminus, which becomes more rigid, upon extension. Since a similar pattern of contacts is observed for other, domains of the immunoglobulin I-set, our results are of general relevance, for this protein family. Our work might also inspire a more rational, approach to the investigation of domain boundaries and their influence on, module stability.
About this StructureAbout this Structure
1NCU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
When a module is also a domain: the role of the N terminus in the stability and the dynamics of immunoglobulin domains from titin., Pfuhl M, Improta S, Politou AS, Pastore A, J Mol Biol. 1997 Jan 17;265(2):242-56. PMID:9020985
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