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EMBO J
2006 Mar 08;255:1035-45. doi: 10.1038/sj.emboj.7601000.
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Structural basis for the inhibition of activin signalling by follistatin.
Harrington AE, Morris-Triggs SA, Ruotolo BT, Robinson CV, Ohnuma S, Hyvönen M.
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The secreted, multidomain protein follistatin binds activins with high affinity, inhibiting their receptor interaction. We have dissected follistatin's domain structure and shown that the minimal activin-inhibiting fragment of follistatin is comprised of the first and second Fs domains (Fs12). This protein can bind to activin dimer and form a stable complex containing two Fs12 molecules and one activin dimer. We have solved crystal structures of activin A alone and its complex with Fs12 fragment to 2 A resolution. The complex structure shows how Fs12 molecules wrap around the back of the 'wings' of activin, blocking the type II receptor-binding site on activin A. Arginine 192 in Fs2 is a key residue in this interaction, inserting itself in between activin's fingers. Complex formation imposes a novel orientation for the EGF- and Kazal-like subdomains in the Fs2 domain and activin A shows further variation from the canonical TGF-beta family fold. The structure provides a detailed description of the inhibitory mechanism and gives insights into interactions of follistatin with other TGF-beta family proteins.
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2002,
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The organizer factors Chordin and Noggin are required for mouse forebrain development.
2000,
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Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers.
2005,
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High-level expression of recombinant genes in Escherichia coli is dependent on the availability of the dnaY gene product.
1989,
Pubmed Brown,
Crystal structure of BMP-9 and functional interactions with pro-region and receptors.
2005,
Pubmed Cho,
Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid.
1991,
Pubmed
,
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Coot: model-building tools for molecular graphics.
2004,
Pubmed Esch,
Structural characterization of follistatin: a novel follicle-stimulating hormone release-inhibiting polypeptide from the gonad.
1987,
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The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4.
1997,
Pubmed
,
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Calculation of protein extinction coefficients from amino acid sequence data.
1989,
Pubmed Glister,
Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells: actions of BMP-4, -6 and -7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin.
2004,
Pubmed Green,
Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.
1992,
Pubmed
,
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A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors.
2004,
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2002,
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Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.
2002,
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Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity.
1994,
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,
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Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40.
1997,
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The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities.
1998,
Pubmed
,
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Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo.
1998,
Pubmed
,
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Crystal structures of the heparan sulfate-binding domain of follistatin. Insights into ligand binding.
2003,
Pubmed Inouye,
Localization of the heparin binding site of follistatin.
1992,
Pubmed James,
TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells.
2005,
Pubmed Keutmann,
The role of follistatin domains in follistatin biological action.
2004,
Pubmed Kirsch,
Crystal structure of the BMP-2-BRIA ectodomain complex.
2000,
Pubmed Mason,
Structure of two human ovarian inhibins.
1986,
Pubmed Massagué,
Transcriptional control by the TGF-beta/Smad signaling system.
2000,
Pubmed Massagué,
TGF-beta signal transduction.
1998,
Pubmed Matzuk,
Functional analysis of activins during mammalian development.
1995,
Pubmed
,
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Refinement of macromolecular structures by the maximum-likelihood method.
1997,
Pubmed Pellegrini,
Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin.
2000,
Pubmed Peränen,
T7 vectors with modified T7lac promoter for expression of proteins in Escherichia coli.
1996,
Pubmed Perrakis,
wARP: improvement and extension of crystallographic phases by weighted averaging of multiple-refined dummy atomic models.
1997,
Pubmed Piccolo,
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
1996,
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,
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Activin redux: specification of mesodermal pattern in Xenopus by graded concentrations of endogenous activin B.
2004,
Pubmed
,
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Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
1994,
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,
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Follistatin-related protein (FSRP): a new member of the follistatin gene family.
2001,
Pubmed Schulte-Merker,
Effects of truncated activin and FGF receptors and of follistatin on the inducing activities of BVg1 and activin: does activin play a role in mesoderm induction?
1994,
Pubmed
,
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Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid.
2005,
Pubmed Shimasaki,
Follistatin gene expression in the ovary and extragonadal tissues.
1989,
Pubmed Sidis,
Heparin and activin-binding determinants in follistatin and FSTL3.
2005,
Pubmed Sidis,
Follistatin: essential role for the N-terminal domain in activin binding and neutralization.
2001,
Pubmed Smith,
Dorsalization and neural induction: properties of the organizer in Xenopus laevis.
1983,
Pubmed
,
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A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies.
2002,
Pubmed Storoni,
Likelihood-enhanced fast rotation functions.
2004,
Pubmed Sugino,
Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell.
1993,
Pubmed Sumitomo,
The heparin binding site of follistatin is involved in its interaction with activin.
1995,
Pubmed Thompson,
Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions.
2003,
Pubmed Tsuchida,
Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-beta family.
2000,
Pubmed Ullman,
The Factor I and follistatin domain families: the return of a prodigal son.
1997,
Pubmed Vassalli,
Activin/inhibin beta B subunit gene disruption leads to defects in eyelid development and female reproduction.
1994,
Pubmed
,
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Analysis of human follistatin structure: identification of two discontinuous N-terminal sequences coding for activin A binding and structural consequences of activin binding to native proteins.
2000,
Pubmed Zimmerman,
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
1996,
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,
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