3U7D

Crystal structure of the KRIT1/CCM1 FERM domain in complex with the heart of glass (HEG1) cytoplasmic tail

3U7D の概要

• エントリーDOI: 10.2210/pdb3u7d/pdb
• 分子名称: Krev interaction trapped protein 1, Protein HEG homolog 1 (3 entities in total)
• 機能のキーワード: psi-biology, assembly, dynamics and evolution of cell-cell and cell-matrix adhesions, cellmat, ferm domain, rap1 effector, membrane protein cytoplasmic tail, protein binding, structural genomics
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: O00522; Isoform 1: Cell membrane; Single-pass type I membrane protein (Potential). Isoform 2: Secreted (Potential): Q9ULI3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 81085.61

構造登録者

Gingras, A.R.,Liu, J.J.,Ginsberg, M.H.,Assembly, Dynamics and Evolution of Cell-Cell and Cell-Matrix Adhesions (CELLMAT) (登録日: 2011-10-13, 公開日: 2012-09-12, 最終更新日: 2024-02-28)

主引用文献

Gingras, A.R.,Liu, J.J.,Ginsberg, M.H.
Structural basis of the junctional anchorage of the cerebral cavernous malformations complex.
J.Cell Biol., 199:39-48, 2012

PubMed Abstract: The products of genes that cause cerebral cavernous malformations (CCM1/KRIT1, CCM2, and CCM3) physically interact. CCM1/KRIT1 links this complex to endothelial cell (EC) junctions and maintains junctional integrity in part by inhibiting RhoA. Heart of glass (HEG1), a transmembrane protein, associates with KRIT1. In this paper, we show that the KRIT1 band 4.1, ezrin, radixin, and moesin (FERM) domain bound the HEG1 C terminus (K(d) = 1.2 µM) and solved the structure of this assembly. The KRIT1 F1 and F3 subdomain interface formed a hydrophobic groove that binds HEG1(Tyr(1,380)-Phe(1,381)), thus defining a new mode of FERM domain-membrane protein interaction. This structure enabled design of KRIT1(L717,721A), which exhibited a >100-fold reduction in HEG1 affinity. Although well folded and expressed, KRIT1(L717,721A) failed to target to EC junctions or complement the effects of KRIT1 depletion on zebrafish cardiovascular development or Rho kinase activation in EC. These data establish that this novel FERM-membrane protein interaction anchors CCM1/KRIT1 at EC junctions to support cardiovascular development.

PubMed: 23007647
DOI: 10.1083/jcb.201205109

実験手法

X-RAY DIFFRACTION (2.49 Å)