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Published on: August 1, 2020
Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch
Hironori Suzuki1, Masato Kawasaki, Tatsutoshi Inuzuka
1Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Structure (London, England : 1993)
|October 23, 2008
Summary
Calcium binding to ALG-2 protein (a penta-EF-hand protein) triggers an arginine switch, enabling interaction with Alix. This mechanism is crucial for endosomal sorting and HIV budding processes.
Area of Science:
- Structural Biology
- Molecular Cell Biology
- Virology
Background:
- The penta-EF-hand (PEF) protein ALG-2 interacts with proteins like Alix and TSG101.
- These interactions are vital for cellular processes including endosomal sorting and HIV budding.
Purpose of the Study:
- To elucidate the structural basis of ALG-2 interactions with Alix.
- To understand the role of calcium ions in ALG-2 function.
Main Methods:
- X-ray crystallography was employed to determine the structures of various ALG-2 forms and its complex with an Alix peptide.
- In vitro binding assays using mutant proteins were conducted.
Main Results:
- Structures of Ca(2+)-free and -bound ALG-2, Zn(2+)-bound ALG-2, and the ALG-2/Alix peptide complex were solved.
- Calcium binding to EF3 repositions Arg125, exposing a hydrophobic pocket for the Alix PPYP motif.
- This binding site partially overlaps with the Cep55 binding motif.
Conclusions:
- A novel Ca(2+)/EF3-driven arginine switch mechanism governs ALG-2 binding to Alix.
- This mechanism provides insight into the regulation of endosomal sorting and viral budding.
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