6O1Q
The N-terminal domain of NPHP1 folds into an antiparallel three-stranded coiled coil
Summary for 6O1Q
| Entry DOI | 10.2210/pdb6o1q/pdb |
| NMR Information | BMRB: 30575 |
| Descriptor | Nephrocystin-1 (1 entity in total) |
| Functional Keywords | nephronophthisis, apoptosis |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13676.49 |
| Authors | Musco, G.,Mannella, V. (deposition date: 2019-02-21, release date: 2019-08-14, Last modification date: 2024-05-01) |
| Primary citation | Mannella, V.,Quilici, G.,Nigro, E.A.,Lampis, M.,Minici, C.,Degano, M.,Boletta, A.,Musco, G. The N-Terminal Domain of NPHP1 Folds into a Monomeric Left-Handed Antiparallel Three-Stranded Coiled Coil with Anti-apoptotic Function. Acs Chem.Biol., 14:1845-1854, 2019 Cited by PubMed Abstract: Mutations in the gene, coding for human nephrocystin-1 (NPHP1), cause the autosomal recessive disease nephronophthisis, the most common cause of end-stage renal disease in children and adolescents. The function and structure of NPHP1 are still poorly characterized. NPHP1 presents a modular structure well in keeping with its role as an adaptor protein: it harbors an SH3 domain flanked by two glutamic acid-rich regions and a conserved C-terminal nephrocystin homology domain (NHD). Similar to other NPHP protein family members, its N-terminus contains a putative coiled-coil domain (NPHP1) that is supposed to play an important role in NPHP1 self-association and/or protein-protein interactions. Structural studies proving its structure and its oligomerization state are still lacking. Here we demonstrate that NPHP1 is monomeric in solution and unexpectedly folds into an autonomous domain forming a three-stranded antiparallel coiled coil suitable for protein-protein interactions. Notably, we found that the NPHP1 shares remarkable structural similarities with the three-stranded coiled coil of the BAG domain protein family, which is known to mediate the anti-apoptotic function of these proteins, suggesting a possible similar role for NPHP1. In agreement with this hypothesis, we show that in the context of the full-length protein the NPHP1 is fundamental to regulate resistance to apoptotic stimuli. PubMed: 31345020DOI: 10.1021/acschembio.9b00582 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
