[대학원 생명과학과 세미나 안내]
연사 : 노성훈 교수 (서울대학교 생명과학부)
연제 : Studying macromolecules through direct imaging; Cryo-EM
일시 : 2019년 3월 22일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 우재성 교수
Abstract
The molecular mechanism of transmembrane proton translocation in rotary motor ATPases is not fully understood. Here we report the 3.5 Å resolution cryoEM structure of the lipid nanodiscreconstituted Vo proton channel of the yeast vacuolar H+-ATPase (V-ATPase), captured in a physiologically relevant, autoinhibited state. The resulting atomic model provides unprecedented detail for the amino acid residues at the interface of the proteolipid ring and the transmembrane portion of subunit a that constitute the proton pathway. Together with previous mutagenesis studies, we propose the chemical basis of transmembrane proton transport. Moreover, we discovered that the C-terminus of the assembly factor Voa1 is an integral component of mature Vo. Voa1’s C-terminal transmembrane α helix is bound inside the proteolipid ring, where it contributes to the stability of the complex. Our structure rationalizes possible mechanisms by which mutations in human Vo can result in disease phenotypes, and may thus provide new avenues for therapeutic interventions.