Your browser doesn't support javascript.
loading
A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
Yan, Renhong; Cao, Pingping; Song, Wenqi; Qian, Hongwu; Du, Ximing; Coates, Hudson W; Zhao, Xin; Li, Yaning; Gao, Shuai; Gong, Xin; Liu, Ximing; Sui, Jianhua; Lei, Jianlin; Yang, Hongyuan; Brown, Andrew J; Zhou, Qiang; Yan, Chuangye; Yan, Nieng.
Afiliación
  • Yan R; Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
  • Cao P; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang Province, China.
  • Song W; State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • Qian H; State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • Du X; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
  • Coates HW; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia.
  • Zhao X; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia.
  • Li Y; State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • Gao S; State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • Gong X; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
  • Liu X; Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
  • Sui J; National Institute of Biological Sciences (NIBS), Beijing 102206, China.
  • Lei J; National Institute of Biological Sciences (NIBS), Beijing 102206, China.
  • Yang H; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China.
  • Brown AJ; Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • Zhou Q; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia.
  • Yan C; School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia.
  • Yan N; Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
Science ; 371(6533)2021 03 05.
Article en En | MEDLINE | ID: mdl-33446483
ABSTRACT
The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1 and -2, are membrane-embedded sterol sensors. The 25-hydroxycholesterol (25HC)-dependent association of Scap and Insig acts as the master switch for the SREBP pathway. Here, we present cryo-electron microscopy analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains determined at an average resolution of 3.7 angstrom. The sterol-sensing domain in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4 to S6 segments in Scap and TMs 3 and 4 in Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos y Proteínas de Señalización Intracelular / Dominios y Motivos de Interacción de Proteínas / Hidroxicolesteroles / Proteínas de la Membrana Límite: Humans Idioma: En Revista: Science Año: 2021 Tipo del documento: Article País de afiliación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos y Proteínas de Señalización Intracelular / Dominios y Motivos de Interacción de Proteínas / Hidroxicolesteroles / Proteínas de la Membrana Límite: Humans Idioma: En Revista: Science Año: 2021 Tipo del documento: Article País de afiliación: China