title: Solution structure of mouse Cripto CFC domain and its inactive variant Trp107Ala.
abstract: We report here for the first time the solution structures at pH 3 and pH 6 of the synthetic CFC domain of mouse Cripto and of the point mutated variant W107A that is unable to bind to the Alk4 Cripto receptor. NMR data confirm that the CFC domain has a C1-C4, C2-C6, C3-C5 disulfide pattern and show that structures are rather flexible and globally extended, with three noncanonical antiparallel strands. His104 and Trp107 side chains protrude from a protein edge and are strongly exposed to solvent, supporting previous evidence of direct involvement in receptor binding. On the opposite molecule side, several nonpolar residues are gathered, forming a large hydrophobic patch that supposedly acts as interface with the cell membrane or the adjacent EGF-like domain. A second hydrophilic patch surrounding His104 and Trp107 is present only in the wild type variant, suggesting a possible involvement in modulating Alk4 recognition.
authors.affiliation: Dipartimento di Chimica, Università Federico II, Complesso Universitario MSA, via Cintia 45, 80126 Napoli, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Calvanese
authors.forename: Angela
authors.initials: A
authors.lastname: Saporito
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Auria
authors.forename: Gabriella
authors.initials: G
authors.lastname: Minchiotti
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Livio
authors.initials: L
authors.lastname: Paolillo
authors.forename: Lucia
authors.initials: L
authors.lastname: Falcigno
authors.forename: Menotti
authors.initials: M
authors.lastname: Ruvo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics; D017354:Point Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012996:Solutions; C489450:Tdgf1 protein, mouse; D004815:Epidermal Growth Factor