PS51847

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

PROSITE profiles entry
Member databasePROSITE profiles
PROSITE profiles typedomain
Short nameSMP

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
[5]
[3]
[4]
[7]
[1]
[6]
. The SMP domain consists of 6 beta-strands and 3 helices arranged to form a barrel whose interior is lined almost exclusively by hydrophobic residues. 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
[7]
[1]
[6]
. The SMP domain belongs to the TULIP (for TUbular LIPid-binding) protein superfamily of lipid transfer proteins
[2]
. 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. - Yeast tricalbins TCB1, TCB2, and TCB3, ER-PM tethers. The profile we developed covers the entire SMP domain.

References

1.ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons. Hirabayashi Y, Kwon SK, Paek H, Pernice WM, Paul MA, Lee J, Erfani P, Raczkowski A, Petrey DS, Pon LA, Polleux F. Science 358, 623-630, (2017). View articlePMID: 29097544

2.Bioinformatics of the TULIP domain superfamily. Kopec KO, Alva V, Lupas AN. Biochem. Soc. Trans. 39, 1033-8, (2011). View articlePMID: 21787343

3.SMP-domain proteins at membrane contact sites: Structure and function. Reinisch KM, De Camilli P. Biochim. Biophys. Acta 1861, 924-927, (2016). View articlePMID: 26686281

4.The Extended-Synaptotagmins. Saheki Y, De Camilli P. Biochim. Biophys. Acta 1864, 1490-1493, (2017). View articlePMID: 28363589

5.Diverse membrane-associated proteins contain a novel SMP domain. Lee I, Hong W. FASEB J. 20, 202-6, (2006). View articlePMID: 16449791

6.Crystal structure of Mdm12 and combinatorial reconstitution of Mdm12/Mmm1 ERMES complexes for structural studies. AhYoung AP, Lu B, Cascio D, Egea PF. Biochem. Biophys. Res. Commun. 488, 129-135, (2017). View articlePMID: 28479252

7.Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer. Schauder CM, Wu X, Saheki Y, Narayanaswamy P, Torta F, Wenk MR, De Camilli P, Reinisch KM. Nature 510, 552-5, (2014). View articlePMID: 24847877

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