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
Some proteins known to contain a SMP domain are listed below:
Metazoan PDZD8, a critical endoplasmic reticulum (ER)-mitochondria
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.
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