8SYM

Human VPS29/VPS35L Complex (Locally refined map)

8SYM の概要

• エントリーDOI: 10.2210/pdb8sym/pdb
• EMDBエントリー: 40884 40885 40886
• 分子名称: VPS35 endosomal protein-sorting factor-like, Vacuolar protein sorting-associated protein 29 (2 entities in total)
• 機能のキーワード: commd, retriever, commander, ccc, protein transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 132738.77

構造登録者

Chen, Z.,Chen, B.,Burstein, E.,Han, Y. (登録日: 2023-05-25, 公開日: 2023-11-01, 最終更新日: 2024-07-03)

主引用文献

Boesch, D.J.,Singla, A.,Han, Y.,Kramer, D.A.,Liu, Q.,Suzuki, K.,Juneja, P.,Zhao, X.,Long, X.,Medlyn, M.J.,Billadeau, D.D.,Chen, Z.,Chen, B.,Burstein, E.
Structural organization of the retriever-CCC endosomal recycling complex.
Nat.Struct.Mol.Biol., 31:910-924, 2024

PubMed Abstract: The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of vacuolar protein-sorting-associated protein (VPS)35L, VPS26C and VPS29, together with the CCC complex comprising coiled-coil domain-containing (CCDC)22, CCDC93 and copper metabolism domain-containing (COMMD) proteins, plays a crucial role in this process. The precise mechanisms underlying retriever assembly and its interaction with CCC have remained elusive. Here, we present a high-resolution structure of retriever in humans determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog retromer. By combining AlphaFold predictions and biochemical, cellular and proteomic analyses, we further elucidate the structural organization of the entire retriever-CCC complex across evolution and uncover how cancer-associated mutations in humans disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with retriever-CCC-mediated endosomal recycling.

PubMed: 38062209
DOI: 10.1038/s41594-023-01184-4

実験手法

ELECTRON MICROSCOPY (3.2 Å)