8A67

Branched Lys48- and Lys63-linked tri-ubiquitin (K48-K63-Ub3) in complex with matured synthetic nanobody NbSL3.3Q (3rd generation)

8A67 の概要

• エントリーDOI: 10.2210/pdb8a67/pdb
• 関連するPDBエントリー: 7NBB 7NPO
• 分子名称: Polyubiquitin-B, Synthetic Nanobody NbSL3.3Q, GLYCEROL, ... (9 entities in total)
• 機能のキーワード: branched ubiquitin, nanobody, complex, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 83368.64

構造登録者

Lange, S.M.,Kulathu, Y. (登録日: 2022-06-16, 公開日: 2023-02-15, 最終更新日: 2024-10-16)

主引用文献

Lange, S.M.,McFarland, M.R.,Lamoliatte, F.,Carroll, T.,Krshnan, L.,Perez-Rafols, A.,Kwasna, D.,Shen, L.,Wallace, I.,Cole, I.,Armstrong, L.A.,Knebel, A.,Johnson, C.,De Cesare, V.,Kulathu, Y.
VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.
Nat.Struct.Mol.Biol., 2024

PubMed Abstract: Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48-K63-branched Ub function. We establish a method to monitor cleavage of linkages within complex Ub chains and unveil ATXN3 and MINDY as debranching enzymes. We engineer a K48-K63 branch-specific nanobody and reveal the molecular basis of its specificity in crystal structures of nanobody-branched Ub chain complexes. Using this nanobody, we detect increased K48-K63-Ub branching following valosin-containing protein (VCP)/p97 inhibition and after DNA damage. Together with our discovery that multiple VCP/p97-associated proteins bind to or debranch K48-K63-linked Ub, these results suggest a function for K48-K63-branched chains in VCP/p97-related processes.

PubMed: 38977901
DOI: 10.1038/s41594-024-01354-y

実験手法

X-RAY DIFFRACTION (1.86 Å)