2arp: Difference between revisions

Revision as of 19:23, 3 May 2008

Activin A in complex with Fs12 fragment of follistatin

OverviewOverview

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.

About this StructureAbout this Structure

2ARP is a Protein complex structure of sequences from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for the inhibition of activin signalling by follistatin., Harrington AE, Morris-Triggs SA, Ruotolo BT, Robinson CV, Ohnuma S, Hyvonen M, EMBO J. 2006 Mar 8;25(5):1035-45. Epub 2006 Feb 16. PMID:16482217 Page seeded by OCA on Sat May 3 19:23:42 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2arp.gif|left|200px]]
- {{Structure
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-|GENE= INHBA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), Fst ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
+-->
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2arp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2arp OCA], [http://www.ebi.ac.uk/pdbsum/2arp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2arp RCSB]</span>
-}}
 '''Activin A in complex with Fs12 fragment of follistatin'''
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 [[Category: Robinson, C V.]]
 [[Category: Ruotolo, B T.]]
-[[Category: cystine knot]]
+[[Category: Cystine knot]]
-[[Category: disulfide rich]]
+[[Category: Disulfide rich]]
-[[Category: egf domain]]
+[[Category: Egf domain]]
-[[Category: kazal domain]]
+[[Category: Kazal domain]]
-[[Category: protein complex]]
+[[Category: Protein complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 19:23:42 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:56:24 2008''