START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins [1]. StAR (Steroidogenic Acute Regulatory protein) is a mitochondrial protein that is synthesised in response to luteinising hormone stimulation [2]. Expression of the protein in the absence of hormone stimulation is sufficient to induce steroid production, suggesting that this protein is required in the acute regulation of steroidogenesis. Representatives of the START domain family havebeen shown to bind different ligands such as sterols (StAR protein) andphosphatidylcholine (PC-TP). Ligand binding by the START domain can alsoregulate the activities of other domains that co-occur with the START domainin multidomain proteins such as Rho-gap, the homeodomain,and the thioesterase domain [3, 3].

The crystal structure of START domain of human MLN64 shows analpha/beta fold built around an U-shaped incomplete beta-barrel. Mostimportantly, the interior of the protein encompasses a 26 x 12 x 11 Angstromshydrophobic tunnel that is apparently large enough to bind a singlecholesterol molecule [4]. The START domain structure revealed an unexpectedsimilarity to that of the birch pollen allergen Bet v 1 and to bacterialpolyketide cyclases/aromatases [5, 5].

1. START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins. Trends Biochem. Sci. 24, 130-2
2. The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J. Biol. Chem. 269, 28314-22
3. Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily. Proteins 43, 134-44
4. Structure and lipid transport mechanism of a StAR-related domain. Nat. Struct. Biol. 7, 408-14

START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling prot
Show more...

Download genes (select columns to include)