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PROSITE documentation PDOC51498 [for PROSITE entry PS51498]

MABP domain profile





Description

A key aspect of eukaryotic intracellular trafficking is the sorting of cell-surface proteins into multi-vesicular endosomes or bodies (MVBs), which eventually fuse with the lysosome, where they are degraded by lipases and peptidases. This is the primary mechanism for down-regulation of signaling via transmembrane receptors and removal of misfolded or defective membrane proteins. This process is also utilized by several viruses (e.g. HIV-1) to facilitate budding of their virions from the cell-membrane. Studies in animals and fungi have shown that it depends on an intricate series of interactions, which is initiated via ubiquitination (typically one or more mono-ubiquitinations) of the cytoplasmic tails of membrane proteins by specific E3 ligases. Ubiquitinated membrane proteins are then captured into endosomes by the ESCRT system and prevented from being recycled back to the plasma membrane via the retrograde trafficking system. The ESCRT system also folds the endosomal membranes into invaginations that are concentrated in these ubiquitinated targets and catalyzes their abscission into intra-luminal-vesicles inside the endosome. This largely seals the fate of these membrane proteins as targets for lysosomal degradation. The ESCRT system is comprised of 4 major protein complexes, ESCRT-0 to ESCRT-III, which are successively involved in the above-described steps [1].

ESCRT-I contains three subunits that are conserved between yeast and animals, namely the inactive E2-ligase protein TSG101/VPS23, VPS28 and VPS37. Additionally, both yeast and metazoan ESCRT-I contain a fourth subunit termed MVB12 (“multivesicular body sorting factor of 12 kD”); however, the MVB12 subunits from the two lineages do not show significant sequence similarity. The metazoan MVB12 proteins contain two distinct conserved domains that occur independently in various proteins. The N-terminal region of MVB12 forms the MVB12-associated β-prism (MABP), which is also found in DENND4A/B/C from vertebrates, the membrane trafficking regulator Crag from Drosophila, bacterial proteins typified by the MAC/perforin (MACPF)-like protein plu1415 from Photorhabdus luminescens and uncharacterized proteins from choanoflagellates and stamenopiles. It has been suggested that the MABP domain has a membrane-associated function, perhaps even specific interactions with membrane components. It is plausible that the eukaryotic MABP domains are adaptators that help linking other associated domains found in the same polypeptide to vesicular membranes [1].

The MABP domain has an internal repeat structure of three homologous segments. Consitent with this, the structurally characterized representative Photorhabdus plu1415, showed that this region precisely corresponds to a type-I β-prism domain with an internal three fold symetry (see <PDB:2QP2>). Each of the three sub-domains of the β-prism structure is a distinctive three-stranded β-sheet. The MABP domain shares a triradial symmetry with β-sheets parallel to the prism axis. The β-prism fold is associated with membrane interaction. The majority of the eukaryotic MABP domain versions contain a conserved cysteine in the first and third subdomain of the β-prism [1,2].

The profile we developed covers the entire MABP domain.

Last update:

June 2010 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

MABP, PS51498; MABP domain profile  (MATRIX)


References

1Authorsde Souza R.F. Aravind L.
TitleUMA and MABP domains throw light on receptor endocytosis and selection of endosomal cargoes.
SourceBioinformatics 0:0-0(2010).
PubMed ID20448139
DOI10.1093/bioinformatics/btq235

2AuthorsRosado C.J. Buckle A.M. Law R.H.P. Butcher R.E. Kan W.-T. Bird C.H. Ung K. Browne K.A. Baran K. Bashtannyk-Puhalovich T.A. Faux N.G. Wong W. Porter C.J. Pike R.N. Ellisdon A.M. Pearce M.C. Bottomley S.P. Emsley J. Smith A.I. Rossjohn J. Hartland E.L. Voskoboinik I. Trapani J.A. Bird P.I. Dunstone M.A. Whisstock J.C.
TitleA common fold mediates vertebrate defense and bacterial attack.
SourceScience 317:1548-1551(2007).
PubMed ID17717151
DOI10.1126/science.1144706



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