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Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Evzen Boura1, James H Hurley

  • 1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 11, 2012
PubMed

Insights

The MVB12-associated β-prism (MABP) domain, found in ESCRT-I, binds acidic lipids and localizes to membranes. Its structure reveals a unique binding patch, explaining its role in cellular processes.

Area of Science:

  • Cell Biology
  • Structural Biology
  • Biochemistry

Background:

  • MVB12-associated β-prism (MABP) domains are predicted in various proteins but lack experimental characterization.
  • The ESCRT-I complex plays roles in endosomal sorting, cytokinesis, and viral budding.

Purpose of the Study:

  • To experimentally characterize the existence, structure, and biochemical properties of MABP domains.
  • To elucidate the function of MABP domains within the ESCRT-I complex.

Main Methods:

  • In vitro binding assays with liposomes of varying acidic lipid content.
  • Subcellular localization studies.
  • Atomic resolution crystal structure determination (1.3 Å) of the MVB12B MABP domain.

Main Results:

  • MABP domains of ESCRT-I subunits (MVB12A and B) bind to liposomes with acidic lipids in a charge-density-dependent manner.
  • MABP domains autonomously localize to subcellular puncta and the plasma membrane.
  • The crystal structure reveals a β-prism fold, a hydrophobic membrane-anchoring loop, and an electropositive phosphoinositide-binding patch.

Conclusions:

  • The MABP domain acts as a functional module sensing acidic lipid charge density.
  • The open basic patch allows for charge-density sensing without stereoselectivity.
  • ESCRT-I functions as a coincidence detector for acidic phospholipids and protein ligands at endosomes and the plasma membrane.

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