Journal article
Interactions of ubiquitin and CHMP5 with the V domain of HD-PTP reveals role for regulation of Vps4 ATPase
Molecular biology of the cell, Vol.32(22), pp.ar42-ar42
12/01/2021
DOI: 10.1091/mbc.E21-04-0219
PMCID: PMC8694081
PMID: 34586919
Abstract
The family of Brol proteins coordinates the activity of the Endosomal Sorting Complexes Required for Transport (ESCRTs) to mediate a number of membrane remodeling events. These events culminate in membrane scission catalyzed by ESCRT-III, whose polymerization and disassembly is controlled by the AAA-ATPase, Vps4. Brol-family members Alix and HD-PTP as well as yeast Brol have central "V" domains that noncovalently bind Ub and connect ubiquitinated proteins to ESCRT-driven functions such as the incorporation of ubiquitinated membrane proteins into intralumenal vesicles of multivesicular bodies. Recently, it was discovered that the V domain of yeast Brol binds the MIT domain of Vps4 to stimulate its ATPase activity. Here we determine the structural basis for how the V domain of human HD-PTP binds ubiquitin. The HD-PTP V domain also binds the MIT domain of Vps4, and ubiquitin binding to the HD-PTP V domain enhances its ability to stimulate Vps4 ATPase activity. Additionally, we found that V domains of both HD-PTP and Brol bind CHMP5 and Vps60, respectively, providing another potential molecular mechanism to alter Vps4 activity. These data support a model whereby contacts between ubiquitin, ESCRT-III, and Vps4 by V domains of the Brol family may coordinate late events in ESCRT-driven membrane remodeling events.
Details
- Title: Subtitle
- Interactions of ubiquitin and CHMP5 with the V domain of HD-PTP reveals role for regulation of Vps4 ATPase
- Creators
- Natalya Pashkova - University of IowaLiping Yu - University of IowaNicholas J. Schnicker - Mayo Clinic in FloridaChun-Che Tseng - Mayo ClinicLokesh Gakhar - Mayo Clinic in FloridaDavid J. Katzmann - University of IowaRobert C. Piper - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.32(22), pp.ar42-ar42
- Publisher
- Amer Soc Cell Biology
- DOI
- 10.1091/mbc.E21-04-0219
- PMID
- 34586919
- PMCID
- PMC8694081
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Number of pages
- 16
- Grant note
- R01 GM116826; R01 GM58202 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/01/2021
- Academic Unit
- Molecular Physiology and Biophysics; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297497702771
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