7NBB
Branched Lys48- and Lys63-linked tri-ubiquitin (K48-K63-Ub3) in complex with synthetic nanobody NbSL3
Summary for 7NBB
| Entry DOI | 10.2210/pdb7nbb/pdb |
| Descriptor | Polyubiquitin-B, Synthetic nanobody NbSL3, MAGNESIUM ION, ... (8 entities in total) |
| Functional Keywords | ubiquitin, branched, heterotypic, nanobody, synthetic nanobody, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 79623.71 |
| Authors | Lange, S.M.,Kulathu, Y. (deposition date: 2021-01-26, release date: 2022-08-10, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 38977901DOI: 10.1038/s41594-024-01354-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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