한빛사논문
- 조회1,593
H. J. Kim1,†,‡, Y. Xu2,†, A. Petri2, K. Vanhoorelbeke3, J. T. B. Crawley2,§,* and J. Emsley1,§,*
1Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, UK.
2Department of Immunology and Inflammation, Imperial College London, London, UK.
3Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
*Corresponding author.
†These authors contributed equally to this work as co-first authors.
‡Present address: College of Pharmacy, Woosuk University, Wanju 55338, Republic of Korea.
§These authors contributed equally to this work as co-last authors.
Abstract
ADAMTS13 is a plasma metalloprotease that is essential for the regulation of von Willebrand factor (VWF) function, mediator of platelet recruitment to sites of blood vessel damage. ADAMTS13 function is dynamically regulated by structural changes induced by VWF binding that convert it from a latent to active conformation. ADAMTS13 global latency is manifest by the interaction of its C-terminal CUB1-2 domains with its central Spacer domain. We resolved the crystal structure of the ADAMTS13 CUB1-2 domains revealing a previously unreported configuration for the tandem CUB domains. Docking simulations between the CUB1-2 domains with the Spacer domain in combination with enzyme kinetic functional characterization of ADAMTS13 CUB domain mutants enabled the mapping of the CUB1-2 domain site that binds the Spacer domain. Together, these data reveal the molecular basis of the ADAMTS13 Spacer-CUB interaction and the control of ADAMTS13 global latency.
논문정보
- Research article
- 2021년 04월 (BRIC 등록일 2021-04-21)
- 국외 연구진
- 의약학 > 약학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
