2ARV

Structure of human Activin A

2ARV の概要

• エントリーDOI: 10.2210/pdb2arv/pdb
• 関連するPDBエントリー: 2ARP
• 分子名称: Inhibin beta A chain, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: homodimer, cystine knot, disulfide linked, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P08476
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26896.57

構造登録者

Harrington, A.E.,Morris-Triggs, S.A.,Ruotolo, B.T.,Robinson, C.V.,Ohnuma, S.,Hyvonen, M. (登録日: 2005-08-22, 公開日: 2006-03-07, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)