2k2y

Solution structure of the folded domain of intermediate IIIa of Tick Carboxypeptidase Inhibitor

spinqualitylabelsall models 2k2y Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2k2y is a 1 chain structure with sequence from Rhipicephalus bursa. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TCI1_RHIBU Publication Abstract from PubMed There is a lack of experimental structural information about folding intermediates of multidomain proteins. Tick carboxypeptidase inhibitor (TCI) is a small, disulfide-rich protein consisting of two domains that fold and unfold autonomously through the formation of two major intermediates, IIIa and IIIb. Each intermediate contains three native disulfide bonds in one domain and six free cysteines in the other domain. Here we have determined the NMR structures of these two intermediates trapped and isolated at acidic pH in which they are stable and compared their structures with that of the native protein analyzed under the same conditions. Both IIIa and IIIb were found to contain a folded region that corresponds to the N- and C-terminal domains of TCI, respectively, with structures very similar to the corresponding regions of the native protein. The remainder of the polypeptide chains of the intermediates was shown to be unfolded in a random coil conformation. Solvent exchange measurements further indicated that the two protein domains are not completely independent, but affect each other in terms of dynamics and stability, in agreement with reported inhibitory activity data. The derived results provide structural evidence for symmetric TCI folding and unfolding mechanisms that converge in IIIa and IIIb and reveal the structural basis that accounts for the strong and simultaneous accumulation of both intermediates. Altogether, this work has important implications for a better understanding of the folding mechanisms of multidomain, disulfide-rich proteins. The NMR structures of the major intermediates of the two-domain tick carboxypeptidase inhibitor reveal symmetry in its folding and unfolding pathways.,Arolas JL, Pantoja-Uceda D, Ventura S, Blanco FJ, Aviles FX J Biol Chem. 2008 Oct 3;283(40):27110-20. Epub 2008 Jul 18. PMID:18640980 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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