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

Valentina Romano; Domenico Raimondo; Luisa Calvanese; Gabriella D’Auria; Anna Tramontano; Lucia Falcigno

doi:10.1007/s00894-012-1370-y

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

Valentina Romano, Domenico Raimondo, Luisa Calvanese, Gabriella D’Auria, Anna Tramontano, Lucia Falcigno

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3617-3625
Number of pages	9
Journal	Journal of Molecular Modeling
Volume	18
Issue number	8
DOIs	https://doi.org/10.1007/s00894-012-1370-y
State	Published - Feb 22 2012
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

Access to Document

10.1007/s00894-012-1370-y

Cite this

@article{374fa21acab74841ac7e91cb4b6a99fd,

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

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. {\textcopyright} Springer-Verlag 2012.",

author = "Valentina Romano and Domenico Raimondo and Luisa Calvanese and Gabriella D{\textquoteright}Auria and Anna Tramontano and Lucia Falcigno",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

year = "2012",

month = feb,

day = "22",

doi = "10.1007/s00894-012-1370-y",

language = "English (US)",

volume = "18",

pages = "3617--3625",

journal = "Journal of Molecular Modeling",

issn = "1610-2940",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "8",

}

TY - JOUR

T1 - Toward a better understanding of the interaction between TGF-β family members and their ALK receptors

AU - Romano, Valentina

AU - Raimondo, Domenico

AU - Calvanese, Luisa

AU - D’Auria, Gabriella

AU - Tramontano, Anna

AU - Falcigno, Lucia

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): KUK-I1-012-43 Acknowledgements: 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. This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2012/2/22

Y1 - 2012/2/22

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/600043

UR - http://link.springer.com/10.1007/s00894-012-1370-y

UR - http://www.scopus.com/inward/record.url?scp=84864716362&partnerID=8YFLogxK

U2 - 10.1007/s00894-012-1370-y

DO - 10.1007/s00894-012-1370-y

M3 - Article

C2 - 22354277

SN - 1610-2940

VL - 18

SP - 3617

EP - 3625

JO - Journal of Molecular Modeling

JF - Journal of Molecular Modeling

IS - 8

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this