Insights into membrane association of the SMP domain of extended synaptotagmin.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 03 2023
Historique:
received: 20 05 2022
accepted: 06 03 2023
entrez: 18 3 2023
pubmed: 19 3 2023
medline: 22 3 2023
Statut: epublish

Résumé

The Synaptotagmin-like Mitochondrial-lipid-binding Protein (SMP) domain is a newly identified lipid transfer module present in proteins that regulate lipid homeostasis at membrane contact sites (MCSs). However, how the SMP domain associates with the membrane to extract and unload lipids is unclear. Here, we performed in vitro DNA brick-assisted lipid transfer assays and in silico molecular dynamics simulations to investigate the molecular basis of the membrane association by the SMP domain of extended synaptotagmin (E-Syt), which tethers the tubular endoplasmic reticulum (ER) to the plasma membrane (PM). We demonstrate that the SMP domain uses its tip region to recognize the extremely curved subdomain of tubular ER and the acidic-lipid-enriched PM for highly efficient lipid transfer. Supporting these findings, disruption of these mechanisms results in a defect in autophagosome biogenesis contributed by E-Syt. Our results suggest a model that provides a coherent picture of the action of the SMP domain at MCSs.

Identifiants

pubmed: 36932127
doi: 10.1038/s41467-023-37202-8
pii: 10.1038/s41467-023-37202-8
pmc: PMC10023780
doi:

Substances chimiques

Synaptotagmins 134193-27-4
Lipids 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1504

Informations de copyright

© 2023. The Author(s).

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Auteurs

Yunyun Wang (Y)

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.

Zhenni Li (Z)

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.

Xinyu Wang (X)

College of Life Sciences, Nankai University, Tianjin, China.

Ziyuan Zhao (Z)

College of Life Sciences, Nankai University, Tianjin, China.

Li Jiao (L)

College of Life Sciences, Nankai University, Tianjin, China.

Ruming Liu (R)

College of Life Sciences, Nankai University, Tianjin, China.

Keying Wang (K)

College of Life Sciences, Zhejiang University, Hangzhou, China.

Rui Ma (R)

College of Physical Science and Technology, Xiamen University, Xiamen, China.

Yang Yang (Y)

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Guo Chen (G)

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.

Yong Wang (Y)

College of Life Sciences, Zhejiang University, Hangzhou, China. yongwang_isb@zju.edu.cn.
The Provincial International Science and Technology Cooperation Base on Engineering Biology, International Campus of Zhejiang University, Haining, China. yongwang_isb@zju.edu.cn.

Xin Bian (X)

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China. xin.bian@nankai.edu.cn.

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Classifications MeSH