6WU5
Human Calcium and Integrin Binding Protein 3
Summary for 6WU5
| Entry DOI | 10.2210/pdb6wu5/pdb |
| Descriptor | Calcium and integrin-binding family member 3, CALCIUM ION, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | ef-hand, dimer, ncs, metal binding protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 45178.98 |
| Authors | Dionne, G.,Shapiro, L. (deposition date: 2020-05-04, release date: 2021-06-23, Last modification date: 2023-10-18) |
| Primary citation | Liang, X.,Qiu, X.,Dionne, G.,Cunningham, C.L.,Pucak, M.L.,Peng, G.,Kim, Y.H.,Lauer, A.,Shapiro, L.,Muller, U. CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells. Neuron, 109:2131-2149.e15, 2021 Cited by PubMed Abstract: CIB2 is a Ca- and Mg-binding protein essential for mechanoelectrical transduction (MET) by cochlear hair cells, but not by vestibular hair cells that co-express CIB2 and CIB3. Here, we show that in cochlear hair cells, CIB3 can functionally substitute for CIB2. Using X-ray crystallography, we demonstrate that CIB2 and CIB3 are structurally similar to KChIP proteins, auxiliary subunits of voltage-gated K4 channels. CIB2 and CIB3 bind to TMC1/2 through a domain in TMC1/2 flanked by transmembrane domains 2 and 3. The co-crystal structure of the CIB-binding domain in TMC1 with CIB3 reveals that interactions are mediated through a conserved CIB hydrophobic groove, similar to KChIP1 binding of K4. Functional studies in mice show that CIB2 regulates TMC1/2 localization and function in hair cells, processes that are affected by deafness-causing CIB2 mutations. We conclude that CIB2 and CIB3 are MET channel auxiliary subunits with striking similarity to K4 channel auxiliary subunits. PubMed: 34089643DOI: 10.1016/j.neuron.2021.05.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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