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Title: Structural basis for membrane targeting by the MVB12-associated [beta]-prism domain of the human ESCRT-I MVB12 subunit

Abstract

MVB12-associated {beta}-prism (MABP) domains are predicted to occur in a diverse set of membrane-associated bacterial and eukaryotic proteins, but their existence, structure, and biochemical properties have not been characterized experimentally. Here, we find that the MABP domains of the MVB12A and B subunits of ESCRT-I are functional modules that bind in vitro to liposomes containing acidic lipids depending on negative charge density. The MABP domain is capable of autonomously localizing to subcellular puncta and to the plasma membrane. The 1.3-{angstrom} atomic resolution crystal structure of the MVB12B MABP domain reveals a {beta}-prism fold, a hydrophobic membrane-anchoring loop, and an electropositive phosphoinositide-binding patch. The basic patch is open, which explains how it senses negative charge density but lacks stereoselectivity. These observations show how ESCRT-I could act as a coincidence detector for acidic phospholipids and protein ligands, enabling it to function both in protein transport at endosomes and in cytokinesis and viral budding at the plasma membrane.

Authors:
;  [1]
  1. NIH
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1034952
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 109; Journal Issue: (6) ; 02, 2012; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; AIDS VIRUS; CHARGE DENSITY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; FUNCTIONALS; IN VITRO; LIPIDS; LIPOSOMES; MEMBRANES; PHOSPHOLIPIDS; PLASMA; PROTEIN STRUCTURE; PROTEINS; RESOLUTION; TRANSPORT

Citation Formats

Boura, Evzen, and Hurley, James H. Structural basis for membrane targeting by the MVB12-associated [beta]-prism domain of the human ESCRT-I MVB12 subunit. United States: N. p., 2012. Web. doi:10.1073/pnas.1117597109.
Boura, Evzen, & Hurley, James H. Structural basis for membrane targeting by the MVB12-associated [beta]-prism domain of the human ESCRT-I MVB12 subunit. United States. https://doi.org/10.1073/pnas.1117597109
Boura, Evzen, and Hurley, James H. 2012. "Structural basis for membrane targeting by the MVB12-associated [beta]-prism domain of the human ESCRT-I MVB12 subunit". United States. https://doi.org/10.1073/pnas.1117597109.
@article{osti_1034952,
title = {Structural basis for membrane targeting by the MVB12-associated [beta]-prism domain of the human ESCRT-I MVB12 subunit},
author = {Boura, Evzen and Hurley, James H},
abstractNote = {MVB12-associated {beta}-prism (MABP) domains are predicted to occur in a diverse set of membrane-associated bacterial and eukaryotic proteins, but their existence, structure, and biochemical properties have not been characterized experimentally. Here, we find that the MABP domains of the MVB12A and B subunits of ESCRT-I are functional modules that bind in vitro to liposomes containing acidic lipids depending on negative charge density. The MABP domain is capable of autonomously localizing to subcellular puncta and to the plasma membrane. The 1.3-{angstrom} atomic resolution crystal structure of the MVB12B MABP domain reveals a {beta}-prism fold, a hydrophobic membrane-anchoring loop, and an electropositive phosphoinositide-binding patch. The basic patch is open, which explains how it senses negative charge density but lacks stereoselectivity. These observations show how ESCRT-I could act as a coincidence detector for acidic phospholipids and protein ligands, enabling it to function both in protein transport at endosomes and in cytokinesis and viral budding at the plasma membrane.},
doi = {10.1073/pnas.1117597109},
url = {https://www.osti.gov/biblio/1034952}, journal = {Proc. Natl. Acad. Sci. USA},
issn = {0027-8424},
number = (6) ; 02, 2012,
volume = 109,
place = {United States},
year = {Thu Mar 15 00:00:00 EDT 2012},
month = {Thu Mar 15 00:00:00 EDT 2012}
}