Solution Structure of Mouse Cripto CFC Domain and Its Inactive Variant Trp107Ala

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• 作者：Luisa Calvanese ; Angela Saporito ; Daniela Marasco ; Gabriella D'Auria ; Gabriella Minchiotti ; Carlo Pedone ; Livio Paolillo ; Lucia Falcigno ; Menotti Ruvo
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：November 30, 2006
• 年：2006
• 卷：49
• 期：24
• 页码：7054 - 7062
• 全文大小：549K
• 年卷期：v.49,no.24(November 30, 2006)
• ISSN：1520-4804

文摘

We report here for the first time the solution structures at pH 3 and pH 6 of the synthetic CFC domain ofmouse 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 thatstructures are rather flexible and globally extended, with three noncanonical antiparallel strands. His104and Trp107 side chains protrude from a protein edge and are strongly exposed to solvent, supporting previousevidence of direct involvement in receptor binding. On the opposite molecule side, several nonpolar residuesare gathered, forming a large hydrophobic patch that supposedly acts as interface with the cell membraneor the adjacent EGF-like domain. A second hydrophilic patch surrounding His104 and Trp107 is presentonly in the wild type variant, suggesting a possible involvement in modulating Alk4 recognition.