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Title: Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport III (ESCRT-III) Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains

Journal Article · · Journal of Biological Chemistry
 [1];  [2]
  1. Univ. of Michigan, Ann Arbor, MI (United States). Life Science Inst.
  2. Univ. of Michigan, Ann Arbor, MI (United States). Medical School. Dept. of Biological Chemistry. Life Science Inst.

The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). In this paper, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. Finally, these observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode.

Research Organization:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); Michigan Economic Development Corp. (United States); Michigan Technology Tri-Corridor (United States)
Grant/Contract Number:
AC02-06CH11357; GM095769; 085P1000817
OSTI ID:
1177441
Journal Information:
Journal of Biological Chemistry, Vol. 290, Issue 13; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 26 works
Citation information provided by
Web of Science

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Cited By (7)

CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis journal June 2018
MAPT/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-III complex formation: a vicious cycle in Alzheimer neurodegeneration journal June 2019
Aquaporin Protein-Protein Interactions journal October 2017
Overgrazing induces alterations in the hepatic proteome of sheep (Ovis aries): an iTRAQ-based quantitative proteomic analysis journal December 2016
Reverse-topology membrane scission by the ESCRT proteins journal October 2016
MAPT/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-III complex formation: a vicious cycle in Alzheimer neurodegeneration text January 2019
MAPT/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-III complex formation: a vicious cycle in Alzheimer neurodegeneration text January 2019