6WUD

Human Calcium and Integrin Binding Protein 3 Bound to TMC1 Residues 303-347

Summary for 6WUD

• Entry DOI: 10.2210/pdb6wud/pdb
• Related: 6wu5 6wu7
• Descriptor: Calcium and integrin-binding family member 3, Transmembrane channel-like protein 1, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: ef-hand, mechanotransduction, hearing, metal binding protein, metal binding-transport protein complex, metal binding/transport protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 28639.59

Authors

Shapiro, L.,Dionne, G. (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

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: 34089643
DOI: 10.1016/j.neuron.2021.05.007

Experimental method

X-RAY DIFFRACTION (1.84 Å)