8XE8
Solution structure of ubiquitin-like domain (UBL) of human ZFAND1
Summary for 8XE8
| Entry DOI | 10.2210/pdb8xe8/pdb |
| Related | 7Y39 |
| Descriptor | AN1-type zinc finger protein 1 (1 entity in total) |
| Functional Keywords | ubiquitin-like domain, ubl, human zfand1, proteasome, stress granule, proteostasis, protein binding |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15679.98 |
| Authors | Lai, C.H.,Ko, K.T.,Fan, P.J.,Yu, T.A.,Chang, C.F.,Hsu, S.T.D. (deposition date: 2023-12-11, release date: 2024-11-20) |
| Primary citation | Lai, C.H.,Ko, K.T.,Fan, P.J.,Yu, T.A.,Chang, C.F.,Draczkowski, P.,Hsu, S.D. Structural insight into the ZFAND1-p97 interaction involved in stress granule clearance. J.Biol.Chem., 300:107230-107230, 2024 Cited by PubMed Abstract: Arsenite-induced stress granule (SG) formation can be cleared by the ubiquitin-proteasome system aided by the ATP-dependent unfoldase p97. ZFAND1 participates in this pathway by recruiting p97 to trigger SG clearance. ZFAND1 contains two An1-type zinc finger domains (ZF1 and ZF2), followed by a ubiquitin-like domain (UBL); but their structures are not experimentally determined. To shed light on the structural basis of the ZFAND1-p97 interaction, we determined the atomic structures of the individual domains of ZFAND1 by solution-state NMR spectroscopy and X-ray crystallography. We further characterized the interaction between ZFAND1 and p97 by methyl NMR spectroscopy and cryo-EM. N spin relaxation dynamics analysis indicated independent domain motions for ZF1, ZF2, and UBL. The crystal structure and NMR structure of UBL showed a conserved β-grasp fold homologous to ubiquitin and other UBLs. Nevertheless, the UBL of ZFAND1 contains an additional N-terminal helix that adopts different conformations in the crystalline and solution states. ZFAND1 uses the C-terminal UBL to bind to p97, evidenced by the pronounced line-broadening of the UBL domain during the p97 titration monitored by methyl NMR spectroscopy. ZFAND1 binding induces pronounced conformational heterogeneity in the N-terminal domain of p97, leading to a partial loss of the cryo-EM density of the N-terminal domain of p97. In conclusion, this work paved the way for a better understanding of the interplay between p97 and ZFAND1 in the context of SG clearance. PubMed: 38537699DOI: 10.1016/j.jbc.2024.107230 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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