2ARP

Activin A in complex with Fs12 fragment of follistatin

Summary for 2ARP

• Entry DOI: 10.2210/pdb2arp/pdb
• Related: 2ARV
• Descriptor: Inhibin beta A chain, Follistatin, NICKEL (II) ION, ... (6 entities in total)
• Functional Keywords: cystine knot, disulfide rich, egf domain, kazal domain, protein complex, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P08476 P21674
• Total number of polymer chains: 2
• Total formula weight: 30381.82

Authors

Harrington, A.E.,Morris-Triggs, S.A.,Ruotolo, B.T.,Robinson, C.V.,Ohnuma, S.,Hyvonen, M. (deposition date: 2005-08-21, release date: 2006-03-07, Last modification date: 2023-08-23)

Primary citation

Harrington, A.E.,Morris-Triggs, S.A.,Ruotolo, B.T.,Robinson, C.V.,Ohnuma, S.,Hyvonen, M.
Structural basis for the inhibition of activin signalling by follistatin
Embo J., 25:1035-1045, 2006

PubMed Abstract: 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.

PubMed: 16482217
DOI: 10.1038/sj.emboj.7601000

Experimental method

X-RAY DIFFRACTION (2 Å)