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| | ==Solution structure of the folded domain of intermediate IIIa of Tick Carboxypeptidase Inhibitor== | | ==Solution structure of the folded domain of intermediate IIIa of Tick Carboxypeptidase Inhibitor== |
| - | <StructureSection load='2k2y' size='340' side='right' caption='[[2k2y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k2y' size='340' side='right'caption='[[2k2y]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k2y]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhipicephalus_bursa Rhipicephalus bursa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K2Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K2Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k2y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhipicephalus_bursa Rhipicephalus bursa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K2Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K2Y FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2k2x|2k2x]], [[2k2z|2k2z]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2y OCA], [https://pdbe.org/2k2y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k2y RCSB], [https://www.ebi.ac.uk/pdbsum/2k2y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k2y ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2y OCA], [http://pdbe.org/2k2y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k2y RCSB], [http://www.ebi.ac.uk/pdbsum/2k2y PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TCI1_RHIBU TCI1_RHIBU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Rhipicephalus bursa]] | | [[Category: Rhipicephalus bursa]] |
| - | [[Category: Blanco, F]] | + | [[Category: Blanco F]] |
| - | [[Category: Pantoja-Uceda, D]] | + | [[Category: Pantoja-Uceda D]] |
| - | [[Category: Blood coagulation]]
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| - | [[Category: Fibrinolysis]]
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| - | [[Category: Hydrolase inhibitor]]
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| - | [[Category: Iiia]]
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| - | [[Category: Metalloenzyme inhibitor]]
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| - | [[Category: Metalloprotease inhibitor]]
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| - | [[Category: Secreted]]
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| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arolas JL, Pantoja-Uceda D, Ventura S, Blanco FJ, Aviles FX. The NMR structures of the major intermediates of the two-domain tick carboxypeptidase inhibitor reveal symmetry in its folding and unfolding pathways. J Biol Chem. 2008 Oct 3;283(40):27110-20. Epub 2008 Jul 18. PMID:18640980 doi:10.1074/jbc.M803978200
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