Phosphatidylserine decarboxylase plays a pivotal role in the synthesis of phospholipid by the mitochondria. The substrate phosphatidylserine is synthesized extramitochondrially and must be translocated to the mitochondria prior to decarboxylation []. Phosphatidylserine decarboxylases is responsible for conversion of phosphatidylserine to phosphatidylethanolamine and plays a central role in the biosynthesis of aminophospholipids [].Phosphatidylserine decarboxylases (PSDs) have been classified in two types. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha and beta subunits [].
Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines [, ]. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning [, , ]. A Shank protein carries scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains.This entry represents the SH3 domain of Shank1 which binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands [].
Myristoylated alanine-rich C-kinase substrate (MARCKS) is a predominentcellular substrate for protein kinase C (PKC) that has been implicated in the regulation of brain development, macrophage activation, neuro-secretion and growth factor-dependentmitogenesis [, ]. The N-terminal glycine is the site of myristoylation, which allows effective binding of the protein to the plasma membrane, whereit co-localises with PKC []. MARCKS binds calmodulin in a calcium-dependentmanner; the region responsible for calcium-binding is highly basic, a domainof about 25 amino acids known as the PSD or effector domain, which also contains the PKCphosphorylation sites and has been shown to contribute to membrane binding. When not phosphorylated, the effector domain can bindto filamentous actin []. It is believed that MARCKS may be a regulated crossbridge between actin and the plasma membrane; modulation of the actincross-linking activity by calmodulin and phosphorylation, represent apotential convergence of the calcium-calmodulin and PKC signal transductionpathways in regulation of the actin cytoskeleton. MARCKS also contains an MH2 domain of unknown function.MARCKS-related protein (MRP) is similar to MARCKS in terms of propertiessuch as its myristoylation, phosphorylation and calmodulin-binding, andshares a high degree of sequence similarity. The two regions that show the highestsimilarity are the kinase C phosphorylation site domain and the N-terminalregion containing the myristoylation site []. MARCKS and MRP amino acid compositions are similar, but the alanine content of the latter is lower. MARCKS proteins appear to adopt a native unfolded conformation i.e. as randomly folded chains arranged in non-classical extended conformations, in common with other substrates of PKC.
