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Updated: Jul 2, 2025
09:51
Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
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Sec7 regulatory domains scaffold autoinhibited and active conformations
Bryce A Brownfield1,2, Brian C Richardson1,2, Steve L Halaby1,2
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
Summary
The study reveals the structure of the autoinhibited Sec7/BIG guanine nucleotide exchange factor (GEF), explaining its inactivity. Researchers also modeled its active form, clarifying how GEF transitions to activate Arf GTPases for Golgi vesicle trafficking.
Area of Science:
- Cell Biology
- Molecular Biology
- Structural Biology
Background:
- Golgi maturation involves vesicle trafficking regulated by Arf GTPases.
- Sec7/BIG guanine nucleotide exchange factors (GEFs) activate Arf GTPases.
- Sec7 activity is modulated by autoinhibition and protein interactions, but its structural basis is unclear.
Purpose of the Study:
- To elucidate the structural mechanisms regulating Sec7/BIG GEF activity.
- To determine the structural basis of Sec7 autoinhibition.
- To model the active conformation of Sec7 for Arf GTPase activation.
Main Methods:
- Cryogenic electron microscopy (cryo-EM) of full-length Sec7.
- Biochemical functional experiments.
- Computational structural predictions.
Main Results:
- Determined the cryo-EM structure of autoinhibited full-length Sec7, detailing its regulatory domains.
- Identified the molecular basis of Sec7 autoinhibition.
- Developed and empirically supported a model for the active conformation of Sec7.
Conclusions:
- The study provides structural insights into Sec7 autoinhibition and activation.
- Elucidates the conformational transition of Sec7 from an inactive to an active state on the organelle membrane.
- Advances understanding of Arf GTPase regulation in Golgi vesicle biogenesis.
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