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Structural investigations on the Nodal‐Cripto binding: A theoretical and experimental approach
Author(s) -
Calvanese Luisa,
Marasco Daniela,
Doti Nunzianna,
Saporito Angela,
D'Auria Gabriella,
Paolillo Livio,
Ruvo Menotti,
Falcigno Lucia
Publication year - 2010
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21517
Subject(s) - nodal , nodal signaling , morphogen , chemistry , homology modeling , computational biology , surface plasmon resonance , epitope , biophysics , microbiology and biotechnology , embryonic stem cell , biology , biochemistry , genetics , nanotechnology , antigen , materials science , gene , gastrulation , nanoparticle , enzyme
Nodal, a member of the transforming growth factor‐β superfamily, is a potent embryonic morphogen also implicated in tumor progression. Up to date structural information on the interaction of Nodal with its molecular partners are unknown. To deepen our understanding about mechanisms underlying both embryonic development and Nodal/Cripto‐dependent tumor progression, we present here a molecular model of activin receptor‐like kinase 4/Cripto/Nodal complex built by homology modeling as well as docking tests aimed at identifying potential binding epitopes. Starting from this model, we have predicted a large interaction surface on Nodal, which encompasses residues 43–69 and includes the prehelix loop and the H3 helix. This hypothesis has been subsequently assessed by surface plasmon resonance binding assays between the full‐length Cripto and synthetic peptides reproducing the selected Nodal regions. In addition, the binding affinity between the full‐length Nodal and Cripto proteins has been evaluated for the first time. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 1011–1021, 2010.