2AK5

beta PIX-SH3 complexed with a Cbl-b peptide

2AK5 の概要

• エントリーDOI: 10.2210/pdb2ak5/pdb
• 分子名称: Rho guanine nucleotide exchange factor 7, 8-residue peptide from a signal transduction protein CBL-B (3 entities in total)
• 機能のキーワード: adaptor proteins, cin85, pix/cool, cbl, protein-protein interaction, endocytosis, endocytosis-exocytosis complex, endocytosis/exocytosis
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cytoplasm: Q13191
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15589.09

構造登録者

Jozic, D.,Cardenes, N.,Deribe, Y.L.,Moncalian, G.,Hoeller, D.,Groemping, Y.,Dikic, I.,Rittinger, K.,Bravo, J. (登録日: 2005-08-03, 公開日: 2005-10-11, 最終更新日: 2023-08-23)

主引用文献

Jozic, D.,Cardenes, N.,Deribe, Y.L.,Moncalian, G.,Hoeller, D.,Groemping, Y.,Dikic, I.,Rittinger, K.,Bravo, J.
Cbl promotes clustering of endocytic adaptor proteins.
Nat.Struct.Mol.Biol., 12:972-979, 2005

PubMed Abstract: The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.

PubMed: 16228008
DOI: 10.1038/nsmb1000

実験手法

X-RAY DIFFRACTION (1.85 Å)