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Sec7 regulatory domains scaffold autoinhibited and active conformations
Bryce A Brownfield1, Brian C Richardson1,2, Steve L Halaby1,3
1Department of Molecular Biology & Genetics and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14850 USA.
Biorxiv : the Preprint Server for Biology
|December 4, 2023
Summary
Researchers elucidated the structural basis for Sec7 activation, a guanine nucleotide exchange factor (GEF) crucial for Golgi vesicle trafficking. Understanding this conformational switch reveals how GEF activity is regulated for proper cell function.
Area of Science:
- Cell Biology
- Structural Biology
- Biochemistry
Background:
- Golgi maturation relies on vesicle trafficking regulated by Arf GTPases.
- Sec7/BIG guanine nucleotide exchange factors (GEFs) activate Arf GTPases for vesicle biogenesis.
- Mechanisms controlling Sec7 localization and activity remain incompletely understood.
Approach:
- Determined the cryo-electron microscopy (cryo-EM) structure of full-length Sec7 in its autoinhibited state.
- Conducted functional experiments to identify the basis of Sec7 autoinhibition.
- Utilized structural predictions to model an empirically supported active conformation of Sec7.
Key Points:
- The cryo-EM structure reveals the architecture of Sec7's regulatory domains in its autoinhibited form.
- Functional data clarifies the molecular mechanisms underlying Sec7 autoinhibition.
- A model for the active conformation of Sec7 provides insights into its activation process.
Conclusions:
- This study elucidates the conformational transition of Sec7 from an autoinhibited to an active state.
- Understanding Sec7's activation mechanism is key to deciphering Golgi trafficking regulation.
- The findings provide a structural basis for how GEFs are activated on organelle membranes.
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