Investigating the oxidative refolding mechanism of Cripto-1 CFC domain(590 views) Iaccarino E, Sandomenico A, Corvino G, Foca G, Severino V, Russo R, Caporale A, Raimondo D, D'Abramo M, Alba J, Chambery A, Ruvo M
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche (DISTABIF), via Vivaldi, 43, 80100 Caserta, Italy
Istituto di Biostrutture e Bioimmagini, CNR and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), via Mezzocannone 16, 80134 Napoli, Italy.
Dipartimento di Medicina Molecolare, Sapienza Universita di Roma, 00161, Italy.
Dipartimento di Chimica, Sapienza Universita di Roma, 00161, Italy.
Anbition srl, via A. Manzoni, 1, 80123 Napoli, Italy. Electronic address: menotti.ruvo@unina.it.
References: Not available.
Investigating the oxidative refolding mechanism of Cripto-1 CFC domain
Using a combined approach based on MS, enzyme digestion and advanced MD studies we have determined the sequential order of formation of the three disulfide bridges of the Cripto-1 CFC domain. The domain has a rare pattern of bridges and is involved in the recognition of several receptors. The bridge formation order is C1-C4, C3-C5, C2-C6, however formation of C1-C4 plays no roles for the formation of the others. Folding is driven by formation of the C3-C5 bridge and is supported by residues lying within the segment delimited by these cysteines. We indeed observe that variants CFC-W123A and CFC-DeltaC1/C4, where C1 and C4 are replaced by serines, are able to refold in the same time window as the wild type, while CFC-K132A and CFC-W134A are not. A variant where cysteines of the second and third bridge are mutated to serine, convert slowly to the monocyclic molecule. Data altogether support a mechanism whereby the Cripto-1 CFC domain refolds by virtue of long-range intramolecular interactions that involve residues close to cysteines of the second and third bridge. These findings are supported by the in silico study that shows how distant parts of the molecules come into contact on a long time scale.
Investigating the oxidative refolding mechanism of Cripto-1 CFC domain
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Investigating the oxidative refolding mechanism of Cripto-1 CFC domain
Kállay C, Dávid A, Timári S, Nagy EM, Sanna D, Garribba E, Micera G, De Bona P, Pappalardo G, Rizzarelli E, Sóvágó I * Copper(II) complexes of rat amylin fragments(572 views) Dalton T (ISSN: 1477-9234, 1477-9226, 1477-9234electronic), 2011 Oct 14; 40(38): 9711-9721. Impact Factor:3.838 ViewExport to BibTeXExport to EndNote
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(564 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote