Structural basis of V-ATPase V O region assembly by Vma12p, 21p, and 22p
| Autor: | Hanlin Wang, Stephanie A. Bueler, John L. Rubinstein |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Proceedings of the National Academy of Sciences. 120 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2217181120 |
| Popis: | Vacuolar-type adenosine triphosphatases (V-ATPases) are rotary proton pumps that acidify specific intracellular compartments in almost all eukaryotic cells. These multi-subunit enzymes consist of a soluble catalytic V 1 region and a membrane-embedded proton-translocating V O region. V O is assembled in the endoplasmic reticulum (ER) membrane, and V 1 is assembled in the cytosol. However, V 1 binds V O only after V O is transported to the Golgi membrane, thereby preventing acidification of the ER. We isolated V O complexes and subcomplexes from Saccharomyces cerevisiae bound to V-ATPase assembly factors Vma12p, Vma21p, and Vma22p. Electron cryomicroscopy shows how the Vma12-22p complex recruits subunits a, e, and f to the rotor ring of V O while blocking premature binding of V 1 . Vma21p, which contains an ER-retrieval motif, binds the V O :Vma12-22p complex, “mature” V O , and a complex that appears to contain a ring of loosely packed rotor subunits and the proteins YAR027W and YAR028W. The structures suggest that Vma21p binds assembly intermediates that contain a rotor ring and that activation of proton pumping following assembly of V 1 with V O removes Vma21p, allowing V-ATPase to remain in the Golgi. Together, these structures show how Vma12-22p and Vma21p function in V-ATPase assembly and quality control, ensuring the enzyme acidifies only its intended cellular targets. |
| Databáze: | OpenAIRE |
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