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PROSITE documentation PDOC51847

Synaptotagmin-like mitochondrial lipid-binding proteins (SMP) domain profile





Description

Membrane contacts sites (MCSs), regions where two organelles come in close proximity to one another, act as molecular hubs for the exchange of small molecules (e.g. lipids) and signals (e.g. calcium ions). Synaptotagmin-like Mitochondrial lipid-binding Proteins (SMP) domains are exclusively found at MCSs between different organelles such as endoplasmic reticulum (ER)-Mitochondrion, ER-Plasma membrane (PM) and Nucleus-Vacuole junctions. The SMP domain is able to homo- or heterodimerize, harbors lipids in a hydrophobic cavity and mediates lipid transfer between the two adjacent bilayers independently of membrane fusion and fission reactions. SMP proteins are widespread amongst eukaryotic species with a particular enrichment in plants and features suggestive of species-specific functional variations. SMP domain-containing proteins have been classified into four broad groups: C2 domain synaptotagmin-like, PH domain-containing HT-008, PDZK8 and mitochondrial protein families [1,2,3,4,5,6].

The SMP domain consists of 6 β-strands and 3 helices arranged to form a barrel whose interior is lined almost exclusively by hydrophobic residues (see <PDB:4P42>). The resulting elongated barrel-shaped cylindrical structure harbors a lateral opening and a central hydrophobic cavity where phospholipids can bind. It dimerizes in an anti-parallel fashion to form a cylinder traversed by a deep hydrophobic groove [4,5,6]. The SMP domain belongs to the TULIP (for TUbular LIPid-binding) protein superfamily of lipid transfer proteins [7].

Some proteins known to contain a SMP domain are listed below:

  • Metazoan PDZD8, a critical endoplasmic reticulum (ER)-mitochondria tethering protein.
  • Yeast Mmmm1, Mdm12, and Mdm34, ER-mitochondria encounter structure (ERMES) complex proteins. The ERMES complex functions as a tether between the ER and mitochondria in yeast.
  • Mammalian Extended-Synaptotagmins (E-SYTs), ER-resident proteins that act as tethers inking the ER and PM membranes into close apposition. Each E-SYT has an amino-terminal ER-membrane anchor, followed by a short linker region, an SMP domain, and three or more C2 domains (see <PDOC00380>).
  • Yeast tricalbins TCB1, TCB2, and TCB3, ER-PM tethers.

The profile we developed covers the entire SMP domain.

Last update:

November 2017 / First entry.

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Technical section

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

SMP, PS51847; Synaptotagmin-like mitochondrial lipid-binding proteins (SMP) domain profile  (MATRIX)


References

1AuthorsLee I. Hong W.
TitleDiverse membrane-associated proteins contain a novel SMP domain.
SourceFASEB J. 20:202-206(2006).
PubMed ID16449791
DOI10.1096/fj.05-4581hyp

2AuthorsReinisch K.M. De Camilli P.
TitleSMP-domain proteins at membrane contact sites: Structure and function.
SourceBiochim. Biophys. Acta. 1861:924-927(2016).
PubMed ID26686281
DOI10.1016/j.bbalip.2015.12.003

3AuthorsSaheki Y. De Camilli P.
TitleThe Extended-Synaptotagmins.
SourceBiochim. Biophys. Acta 1864:1490-1493(2017).
PubMed ID28363589
DOI10.1016/j.bbamcr.2017.03.013

4AuthorsSchauder C.M. Wu X. Saheki Y. Narayanaswamy P. Torta F. Wenk M.R. De Camilli P. Reinisch K.M.
TitleStructure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer.
SourceNature 510:552-555(2014).
PubMed ID24847877
DOI10.1038/nature13269

5AuthorsHirabayashi Y. Kwon S.-K. Paek H. Pernice W.M. Paul M.A. Lee J. Erfani P. Raczkowski A. Petrey D.S. Pon L.A. Polleux F.
TitleER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons.
SourceScience 358:623-630(2017).
PubMed ID29097544
DOI10.1126/science.aan6009

6AuthorsAhYoung A.P. Lu B. Cascio D. Egea P.F.
TitleCrystal structure of Mdm12 and combinatorial reconstitution of Mdm12/Mmm1 ERMES complexes for structural studies.
SourceBiochem. Biophys. Res. Commun. 488:129-135(2017).
PubMed ID28479252
DOI10.1016/j.bbrc.2017.05.021

7AuthorsKopec K.O. Alva V. Lupas A.N.
TitleBioinformatics of the TULIP domain superfamily.
SourceBiochem. Soc. Trans. 39:1033-1038(2011).
PubMed ID21787343
DOI10.1042/BST0391033



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