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-Structure paper
タイトル | MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels. |
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ジャーナル・号・ページ | Science, Vol. 381, Issue 6659, Page 799-804, Year 2023 |
掲載日 | 2023年8月18日 |
著者 | Zijing Zhou / Xiaonuo Ma / Yiechang Lin / Delfine Cheng / Navid Bavi / Genevieve A Secker / Jinyuan Vero Li / Vaibhao Janbandhu / Drew L Sutton / Hamish S Scott / Mingxi Yao / Richard P Harvey / Natasha L Harvey / Ben Corry / Yixiao Zhang / Charles D Cox / |
PubMed 要旨 | Piezo channels are critical cellular sensors of mechanical forces. Despite their large size, ubiquitous expression, and irreplaceable roles in an ever-growing list of physiological processes, few ...Piezo channels are critical cellular sensors of mechanical forces. Despite their large size, ubiquitous expression, and irreplaceable roles in an ever-growing list of physiological processes, few Piezo channel-binding proteins have emerged. In this work, we found that MyoD (myoblast determination)-family inhibitor proteins (MDFIC and MDFI) are PIEZO1/2 interacting partners. These transcriptional regulators bind to PIEZO1/2 channels, regulating channel inactivation. Using single-particle cryogenic electron microscopy, we mapped the interaction site in MDFIC to a lipidated, C-terminal helix that inserts laterally into the PIEZO1 pore module. These Piezo-interacting proteins fit all the criteria for auxiliary subunits, contribute to explaining the vastly different gating kinetics of endogenous Piezo channels observed in many cell types, and elucidate mechanisms potentially involved in human lymphatic vascular disease. |
リンク | Science / PubMed:37590348 |
手法 | EM (単粒子) |
解像度 | 3.56 - 3.86 Å |
構造データ | EMDB-35577, PDB-8imz: EMDB-36241: Cryo-EM structure of mouse Piezo1-MDFIC complex (consensus map) EMDB-36242: Cryo-EM structure of mouse Piezo1-MDFIC complex (Masked refinement of the cap domain) EMDB-36243: Cryo-EM structure of mouse Piezo1-MDFIC complex (masked refinement of the transmembrane domain) EMDB-36244: Cryo-EM structure of mouse Piezo1-MDFIC(C240A) complex |
由来 |
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キーワード | MEMBRANE PROTEIN / Piezo1 complex / mechanosensation / mechanotransduction |