Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560

Xuefei Guo; Yumeng Wang; Jiayao Zhou; Chen Jin; Jiaoni Wang; Bojun Jia; Dan Jing; Chuangye Yan; Jianlin Lei; Rui Zhou; Yigong Shi

doi:10.1038/s41467-022-33817-5

Nature Communications (Oct 2022)

Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560

Xuefei Guo,
Yumeng Wang,
Jiayao Zhou,
Chen Jin,
Jiaoni Wang,
Bojun Jia,
Dan Jing,
Chuangye Yan,
Jianlin Lei,
Rui Zhou,
Yigong Shi

Affiliations

Xuefei Guo: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Yumeng Wang: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Jiayao Zhou: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Chen Jin: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Jiaoni Wang: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Bojun Jia: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Dan Jing: Westlake Laboratory of Life Science and Biomedicine, Xihu District
Chuangye Yan: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Jianlin Lei: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Rui Zhou: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University
Yigong Shi: Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University

DOI: https://doi.org/10.1038/s41467-022-33817-5
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 7

Abstract

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Presenilin isoforms (PS1 and PS2) containing γ-secretase show contrasting sensitivity to MRK-560. Here, the authors determined cryo-EM structures of PS1/PS2-complexes treated with MRK-560 and identified key residues responsible for the isoform-dependent selectivity.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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