한빛사논문
- 조회1,158
Do Hoon Kwon1, Feng Zhang1, Justin G. Fedor1, Yang Suo1 & Seok-Yong Lee1,*
1Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
*Corresponding author.
Abstract
Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods and cryo-EM in an attempt to obtain temporal resolution of the conformational trajectory of the vanilloid receptor TRPV1 with resiniferatoxin (RTx) bound. Based on our cryo-EM ensemble analysis, RTx binding to TRPV1 appears to induce intracellular gate opening first, followed by selectivity filter dilation, then pore loop rearrangement to reach the final open state. This apparent conformational wave likely arises from the concerted, stepwise, additive structural changes of TRPV1 over many subdomains. Greater understanding of the RTx-mediated long-range allostery of TRPV1 could help further the therapeutic potential of RTx, which is a promising drug candidate for pain relief associated with advanced cancer or knee arthritis.
논문정보
- Research article
- 2022년 05월 (BRIC 등록일 2022-05-31)
- 국외 연구진
- 생명과학 > 생화학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
