A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols-Reference-Cited by-同舟云学术

A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols

Published:2021-03-05 Issue:6533 Volume:371 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Yan Renhong¹²^ORCID,Cao Pingping³^ORCID,Song Wenqi³^ORCID,Qian Hongwu⁴,Du Ximing⁵^ORCID,Coates Hudson W.⁵^ORCID,Zhao Xin³^ORCID,Li Yaning³,Gao Shuai⁴^ORCID,Gong Xin⁶,Liu Ximing⁷,Sui Jianhua⁷⁸^ORCID,Lei Jianlin⁹^ORCID,Yang Hongyuan⁵^ORCID,Brown Andrew J.⁵^ORCID,Zhou Qiang¹²^ORCID,Yan Chuangye³,Yan Nieng⁴^ORCID

Affiliation:

1. 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.

2. Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang Province, China.

3. 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.

4. Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

5. School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW 2052, Australia.

6. Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

7. National Institute of Biological Sciences (NIBS), Beijing 102206, China.

8. Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China.

9. Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Abstract

A cellular cholesterol sensor Cholesterol levels in cells are controlled by the sterol regulatory element–binding protein (SREBP) pathway. When the cell has sufficient cholesterol, the transcription factor that regulates cholesterol metabolism is sequestered at the endoplasmic reticulum membrane, but when cholesterol is depleted, the transcription factor is released to activate the expression of genes involved in cholesterol synthesis and uptake. Yan et al. determined the structure of a central complex in human SREBP containing the proteins Scap and Insig-2. These two membrane-embedded proteins undergo 25-hydroxycholesterol (25HC)–dependent association and must dissociate for the pathway to be activated. The structure shows that 25HC is sandwiched between Scap and Insig-2 to facilitate their association. A mutational analysis is consistent with the structural model. Science , this issue p. eabb2224

Funder

National Natural Science Foundation of China

Ministry of Science and Technology of the People’s Republic of China

China Postdoctoral Science Foundation

Beijing Nova Program

National Postdoctoral Program for Innovative Talents of China

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference67 articles.

1. The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor