7WJT

Crystal structure of coiled-coil region of mouse TMEM266

Summary for 7WJT

• Entry DOI: 10.2210/pdb7wjt/pdb
• Descriptor: Isoform 2 of Transmembrane protein 266 (1 entity in total)
• Functional Keywords: voltage-sensor protein, membrane protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 4
• Total formula weight: 29232.80

Authors

Narita, H.,Nishikawa, S.,Nakagawa, A. (deposition date: 2022-01-07, release date: 2022-10-26, Last modification date: 2024-10-23)

Primary citation

Kawai, T.,Narita, H.,Konno, K.,Akter, S.,Andriani, R.T.,Iwasaki, H.,Nishikawa, S.,Yokoi, N.,Fukata, Y.,Fukata, M.,Wiriyasermkul, P.,Kongpracha, P.,Nagamori, S.,Takao, K.,Miyakawa, T.,Abe, M.,Sakimura, K.,Watanabe, M.,Nakagawa, A.,Okamura, Y.
Insight into the function of a unique voltage-sensor protein (TMEM266) and its short form in mouse cerebellum.
Biochem.J., 479:1127-1145, 2022

PubMed Abstract: Voltage-sensing proteins generally consist of voltage-sensor domains and pore-gate domains, forming the voltage-gated ion channels. However, there are several unconventional voltage-sensor proteins that lack pore-gate domains, conferring them unique voltage-sensing machinery. TMEM266, which is expressed in cerebellum granule cells, is one of the interesting voltage-sensing proteins that has a putative intracellular coiled-coil and a functionally unidentified cytosolic region instead of a pore-gate domain. Here, we approached the molecular function of TMEM266 by performing co-immunoprecipitation experiments. We unexpectedly discovered that TMEM266 proteins natively interact with the novel short form splice variants that only have voltage-sensor domains and putative cytosolic coiled-coil region in cerebellum. The crystal structure of coiled-coil region of TMEM266 suggested that these coiled-coil regions play significant roles in forming homodimers. In vitro expression experiments supported the idea that short form TMEM266 (sTMEM266) or full length TMEM266 (fTMEM266) form homodimers. We also performed proximity labeling mass spectrometry analysis for fTMEM266 and sTMEM266 using Neuro-2A, neuroblastoma cells, and fTMEM266 showed more interacting molecules than sTMEM266, suggesting that the C-terminal cytosolic region in fTMEM266 binds to various targets. Finally, TMEM266-deficient animals showed the moderate abnormality in open-field test. The present study provides clues about the novel voltage-sensing mechanism mediated by TMEM266.

PubMed: 35574701
DOI: 10.1042/BCJ20220033

Experimental method

X-RAY DIFFRACTION (2.3 Å)