8CDS
Crystal structure of the xhNup93-Nb4i VHH antibody
Summary for 8CDS
| Entry DOI | 10.2210/pdb8cds/pdb |
| Descriptor | 5-Nup93 inhibitory VHH antibody, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (4 entities in total) |
| Functional Keywords | inhibitory vhh antibody, nanobody, immune system |
| Biological source | Vicugna pacos (Alpaca) |
| Total number of polymer chains | 1 |
| Total formula weight | 14066.65 |
| Authors | Guttler, T.,Colom, M.S.,Gorlich, D. (deposition date: 2023-02-01, release date: 2024-02-21, Last modification date: 2024-06-12) |
| Primary citation | Sola Colom, M.,Fu, Z.,Gunkel, P.,Guttler, T.,Trakhanov, S.,Srinivasan, V.,Gregor, K.,Pleiner, T.,Gorlich, D. A checkpoint function for Nup98 in nuclear pore formation suggested by novel inhibitory nanobodies. Embo J., 43:2198-2232, 2024 Cited by PubMed Abstract: Nuclear pore complex (NPC) biogenesis is a still enigmatic example of protein self-assembly. We now introduce several cross-reacting anti-Nup nanobodies for imaging intact nuclear pore complexes from frog to human. We also report a simplified assay that directly tracks postmitotic NPC assembly with added fluorophore-labeled anti-Nup nanobodies. During interphase, NPCs are inserted into a pre-existing nuclear envelope. Monitoring this process is challenging because newly assembled NPCs are indistinguishable from pre-existing ones. We overcame this problem by inserting Xenopus-derived NPCs into human nuclear envelopes and using frog-specific anti-Nup nanobodies for detection. We further asked whether anti-Nup nanobodies could serve as NPC assembly inhibitors. Using a selection strategy against conserved epitopes, we obtained anti-Nup93, Nup98, and Nup155 nanobodies that block Nup-Nup interfaces and arrest NPC assembly. We solved structures of nanobody-target complexes and identified roles for the Nup93 α-solenoid domain in recruiting Nup358 and the Nup214·88·62 complex, as well as for Nup155 and the Nup98 autoproteolytic domain in NPC scaffold assembly. The latter suggests a checkpoint linking pore formation to the assembly of the Nup98-dominated permeability barrier. PubMed: 38649536DOI: 10.1038/s44318-024-00081-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.53 Å) |
Structure validation
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