Toward a better understanding of the interaction between TGF-β family members and their ALK receptors

Handle URI:
http://hdl.handle.net/10754/600043
Title:
Toward a better understanding of the interaction between TGF-β family members and their ALK receptors
Authors:
Romano, Valentina; Raimondo, Domenico; Calvanese, Luisa; D’Auria, Gabriella; Tramontano, Anna; Falcigno, Lucia
Abstract:
Transforming growth factor-beta (TGF-β) proteins are a family of structurally related extracellular proteins that trigger their signaling functions through interaction with the extracellular domains of their cognate serine/threonine kinase receptors. The specificity of TGF-β/receptor binding is complex and gives rise to multiple functional roles. Additionally, it is not completely understood at the atomic level. Here, we use the most reliable computational methods currently available to study systems involving activin-like kinase (ALK) receptors ALK4 and ALK7 and their multiple TGF-β ligands. We built models for all these proteins and their complexes for which experimental structures are not available. By analyzing the surfaces of interaction in six different TGF-β/ALK complexes we could infer which are the structural distinctive features of the ligand-receptor binding mode. Furthermore, this study allowed us to rationalize why binding of the growth factors GDF3 and Nodal to the ALK4 receptor requires the Cripto co-factor, whilst binding to the ALK7 receptor does not. © Springer-Verlag 2012.
Citation:
Romano V, Raimondo D, Calvanese L, D’Auria G, Tramontano A, et al. (2012) Toward a better understanding of the interaction between TGF-β family members and their ALK receptors. J Mol Model 18: 3617–3625. Available: http://dx.doi.org/10.1007/s00894-012-1370-y.
Publisher:
Springer Nature
Journal:
Journal of Molecular Modeling
KAUST Grant Number:
KUK-I1-012-43
Issue Date:
22-Feb-2012
DOI:
10.1007/s00894-012-1370-y
PubMed ID:
22354277
Type:
Article
ISSN:
1610-2940; 0948-5023
Sponsors:
King Abdullah University of Science and Technology (KAUST; Award No. KUK-I1-012-43); Fondazione Roma and the Italian Ministry of Health (contract no. onc_ord 25/07, FIRB ITAL-BIONET and PROTEOMICA).Ministero dell'Universita e della Ricerca Scientifica (MIUR), project PRIN no prot. 2008F5A3AF_001.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorRomano, Valentinaen
dc.contributor.authorRaimondo, Domenicoen
dc.contributor.authorCalvanese, Luisaen
dc.contributor.authorD’Auria, Gabriellaen
dc.contributor.authorTramontano, Annaen
dc.contributor.authorFalcigno, Luciaen
dc.date.accessioned2016-02-28T06:34:55Zen
dc.date.available2016-02-28T06:34:55Zen
dc.date.issued2012-02-22en
dc.identifier.citationRomano V, Raimondo D, Calvanese L, D’Auria G, Tramontano A, et al. (2012) Toward a better understanding of the interaction between TGF-β family members and their ALK receptors. J Mol Model 18: 3617–3625. Available: http://dx.doi.org/10.1007/s00894-012-1370-y.en
dc.identifier.issn1610-2940en
dc.identifier.issn0948-5023en
dc.identifier.pmid22354277en
dc.identifier.doi10.1007/s00894-012-1370-yen
dc.identifier.urihttp://hdl.handle.net/10754/600043en
dc.description.abstractTransforming growth factor-beta (TGF-β) proteins are a family of structurally related extracellular proteins that trigger their signaling functions through interaction with the extracellular domains of their cognate serine/threonine kinase receptors. The specificity of TGF-β/receptor binding is complex and gives rise to multiple functional roles. Additionally, it is not completely understood at the atomic level. Here, we use the most reliable computational methods currently available to study systems involving activin-like kinase (ALK) receptors ALK4 and ALK7 and their multiple TGF-β ligands. We built models for all these proteins and their complexes for which experimental structures are not available. By analyzing the surfaces of interaction in six different TGF-β/ALK complexes we could infer which are the structural distinctive features of the ligand-receptor binding mode. Furthermore, this study allowed us to rationalize why binding of the growth factors GDF3 and Nodal to the ALK4 receptor requires the Cripto co-factor, whilst binding to the ALK7 receptor does not. © Springer-Verlag 2012.en
dc.description.sponsorshipKing Abdullah University of Science and Technology (KAUST; Award No. KUK-I1-012-43); Fondazione Roma and the Italian Ministry of Health (contract no. onc_ord 25/07, FIRB ITAL-BIONET and PROTEOMICA).Ministero dell'Universita e della Ricerca Scientifica (MIUR), project PRIN no prot. 2008F5A3AF_001.en
dc.publisherSpringer Natureen
dc.subjectALK receptoren
dc.subjectComparative modelingen
dc.subjectProtein-protein dockingen
dc.subjectTGF-β proteinen
dc.titleToward a better understanding of the interaction between TGF-β family members and their ALK receptorsen
dc.typeArticleen
dc.identifier.journalJournal of Molecular Modelingen
dc.contributor.institutionUniversita degli Studi di Napoli Federico II, Naples, Italyen
dc.contributor.institutionUniversita degli Studi di Roma La Sapienza, Rome, Italyen
dc.contributor.institutionConsiglio Nazionale delle Ricerche, Rome, Italyen
kaust.grant.numberKUK-I1-012-43en

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