Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
