START (StAR-related lipid-transfer) is a lipid-binding domain in StAR, HD-ZIP and signalling proteins.[1] The archetypical domain is found in StAR (Steroidogenic acute regulatory protein), a mitochondrial protein that is synthesized in steroid-producing cells.[2] StAR initiates steroid production by mediating the delivery of cholesterol to the first enzyme in the steroidogenic pathway. The START domain is critical for this activity, perhaps through the binding of cholesterol. Following the discovery of StAR, 15 START-domain-containing proteins (termed STARD1 through STARD15) were subsequently identified in vertebrates as well as other that are related.
Thousands of proteins containing at least one START domain have been determined in invertebrates, bacteria and plants to form a larger superfamily, variously known as START, Bet v1-like or SRPBCC (START/RHOalphaC/PITP/Bet v1/CoxG/CalC) domain proteins, all of which bind hydrophobic ligands. In the case of plants, many of the START proteins fall into the category of putative lipid/sterol-binding homeodomain (HD) transcription factors or HD-START proteins.[3]
Representatives of the START domain family bind different substances or ligands such as sterols (e.g., StAR or STARD1) and lipids like phosphatidylcholine (phosphatidylcholine transfer protein, also called PCTP or STARD2) and have enzymatic activities. Ligand binding by the START domain in multidomain proteins can also regulate the activities of the other domains, such as the RhoGAP domain, the homeodomain and the thioesterase domain.[1][4]
The crystal structure of START domain of human MLN64 shows an alpha/beta fold built around a U-shaped incomplete beta-barrel. Most importantly, the interior of the protein encompasses a 26 × 12 × 11-Angstrom hydrophobic tunnel that is apparently large enough to bind a single cholesterol molecule.[5] The START domain structure revealed an unexpected similarity to that of the birch pollen allergen Bet v 1 and to bacterial polyketidecyclases/aromatases.[4][5]
Human proteins containing the START domainedit
START domain-containing proteins in the human are divided into five subfamilies. An exception is StarD9 whose activity remains unknown. Other proteins also exist in the human with domains that are members of the START-based superfamily such as PITP, but are not part of the START domain itself.
Mutations in STAR D9 (KIF16A) have been associated with a syndrome that includes severe ID, characteristic features, epilepsy, acquired microcephaly, and blindness.[6] The STAR D9 gene encodes a 4.7 kilodalton amino acid protein which is a member of the kinesin superfamily. C-terminally truncated STAR D9 mutants are known from experimental work to induce spindle assembly defects. In the reported case, several mitotic defects including multipolar spindle formation, fragmentation of pericentriolar materials, and centrosome amplification were found.
^ abPonting CP, Aravind L (1999). "START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins". Trends Biochem. Sci. 24 (4): 130–132. doi:10.1016/S0968-0004(99)01362-6. PMID 10322415.
^Clark BJ, Wells J, King SR, Stocco DM (1994). "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 (45): 28314–28322. doi:10.1016/S0021-9258(18)46930-X. PMID 7961770.
^Schrick K, Nguyen D, Karlowski WM, Mayer KF (2004). "START lipid/sterol-binding domains are amplified in plants and are predominantly associated with homeodomain transcription factors". Genome Biol. 5 (6): R41. doi:10.1186/gb-2004-5-6-r41. PMC463074. PMID 15186492.
^ abKoonin EV, Aravind L, Iyer LM (2001). "Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily". Proteins. 43 (2): 134–144. doi:10.1002/1097-0134(20010501)43:2<134::AID-PROT1025>3.0.CO;2-I. PMID 11276083. S2CID 6322401.
^ abHurley JH, Tsujishita Y (2000). "Structure and lipid transport mechanism of a StAR-related domain". Nat. Struct. Biol. 7 (5): 408–414. doi:10.1038/75192. PMID 10802740. S2CID 10806665.
^Okamoto N, Tsuchiya Y, Miya F, Tsunoda T, Yamashita K, Boroevich KA, Kato M, Saitoh S, Yamasaki M, Kanemura Y, Kosaki K, Kitagawa D (2017) A novel genetic syndrome with STARD9 mutation and abnormal spindle morphology. Am J Med Genet
This article incorporates text from the public domain Pfam and InterPro: IPR002913
January 01, 1970
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START StAR related lipid transfer is a lipid binding domain in StAR HD ZIP and signalling proteins 1 The archetypical domain is found in StAR Steroidogenic acute regulatory protein a mitochondrial protein that is synthesized in steroid producing cells 2 StAR initiates steroid production by mediating the delivery of cholesterol to the first enzyme in the steroidogenic pathway The START domain is critical for this activity perhaps through the binding of cholesterol Following the discovery of StAR 15 START domain containing proteins termed STARD1 through STARD15 were subsequently identified in vertebrates as well as other that are related STARTstar related lipid transport domain of mln64IdentifiersSymbolSTARTPfamPF01852Pfam clanCL0209InterProIPR002913SMARTSTARTSCOP21em2 SCOPe SUPFAMOPM superfamily138OPM protein1ln1Membranome564Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary START domainIdentifiersSymbolSTARTPfamPF01852InterProIPR002913SMARTSTARTSCOP21em2 SCOPe SUPFAMTCDB9 B 64CDDcd00177Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summary Thousands of proteins containing at least one START domain have been determined in invertebrates bacteria and plants to form a larger superfamily variously known as START Bet v1 like or SRPBCC START RHOalphaC PITP Bet v1 CoxG CalC domain proteins all of which bind hydrophobic ligands In the case of plants many of the START proteins fall into the category of putative lipid sterol binding homeodomain HD transcription factors or HD START proteins 3 Representatives of the START domain family bind different substances or ligands such as sterols e g StAR or STARD1 and lipids like phosphatidylcholine phosphatidylcholine transfer protein also called PCTP or STARD2 and have enzymatic activities Ligand binding by the START domain in multidomain proteins can also regulate the activities of the other domains such as the RhoGAP domain the homeodomain and the thioesterase domain 1 4 Contents 1 Structure 2 Human proteins containing the START domain 2 1 Cholesterol oxysterol binding StarD1 D3 subfamily 2 2 StarD4 subfamily 2 3 Phospholipid sphingolipid binding StarD2 subfamily 2 4 SAM RhoGAP START subfamily 2 5 Acyl CoA thioesterase subfamily 3 See also 4 ReferencesStructure editThe crystal structure of START domain of human MLN64 shows an alpha beta fold built around a U shaped incomplete beta barrel Most importantly the interior of the protein encompasses a 26 12 11 Angstrom hydrophobic tunnel that is apparently large enough to bind a single cholesterol molecule 5 The START domain structure revealed an unexpected similarity to that of the birch pollen allergen Bet v 1 and to bacterial polyketide cyclases aromatases 4 5 Human proteins containing the START domain editSTART domain containing proteins in the human are divided into five subfamilies An exception is StarD9 whose activity remains unknown Other proteins also exist in the human with domains that are members of the START based superfamily such as PITP but are not part of the START domain itself Mutations in STAR D9 KIF16A have been associated with a syndrome that includes severe ID characteristic features epilepsy acquired microcephaly and blindness 6 The STAR D9 gene encodes a 4 7 kilodalton amino acid protein which is a member of the kinesin superfamily C terminally truncated STAR D9 mutants are known from experimental work to induce spindle assembly defects In the reported case several mitotic defects including multipolar spindle formation fragmentation of pericentriolar materials and centrosome amplification were found Cholesterol oxysterol binding StarD1 D3 subfamily edit These proteins are primarily concerned with cholesterol transport StAR STARD1 MLN64 STARD3 StarD4 subfamily edit These proteins are involved in cholesterol and oxysterol transport STARD4 STARD5 STARD6 Phospholipid sphingolipid binding StarD2 subfamily edit Phosphatidylcholine transfer protein PCTP STARD2 STARD7 STARD10 Collagen type IV alpha 3 binding protein COL4A3BP Ceramide transfer protein CERT STARD11 SAM RhoGAP START subfamily edit These proteins contain both the START domain and Rho GTPase signaling activity STARD8 DLC 3 DLC1 STARD12 STARD13 DLC 2 Acyl CoA thioesterase subfamily edit The members of this subfamily possess the START domain and thioesterase activity ACOT11 STARD14 ACOT12 STARD15 See also editSterol carrier proteinReferences edit a b Ponting CP Aravind L 1999 START a lipid binding domain in StAR HD ZIP and signalling proteins Trends Biochem Sci 24 4 130 132 doi 10 1016 S0968 0004 99 01362 6 PMID 10322415 Clark BJ Wells J King SR Stocco DM 1994 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 45 28314 28322 doi 10 1016 S0021 9258 18 46930 X PMID 7961770 Schrick K Nguyen D Karlowski WM Mayer KF 2004 START lipid sterol binding domains are amplified in plants and are predominantly associated with homeodomain transcription factors Genome Biol 5 6 R41 doi 10 1186 gb 2004 5 6 r41 PMC 463074 PMID 15186492 a b Koonin EV Aravind L Iyer LM 2001 Adaptations of the helix grip fold for ligand binding and catalysis in the START domain superfamily Proteins 43 2 134 144 doi 10 1002 1097 0134 20010501 43 2 lt 134 AID PROT1025 gt 3 0 CO 2 I PMID 11276083 S2CID 6322401 a b Hurley JH Tsujishita Y 2000 Structure and lipid transport mechanism of a StAR related domain Nat Struct Biol 7 5 408 414 doi 10 1038 75192 PMID 10802740 S2CID 10806665 Okamoto N Tsuchiya Y Miya F Tsunoda T Yamashita K Boroevich KA Kato M Saitoh S Yamasaki M Kanemura Y Kosaki K Kitagawa D 2017 A novel genetic syndrome with STARD9 mutation and abnormal spindle morphology Am J Med Genet This article incorporates text from the public domain Pfam and InterPro IPR002913 Retrieved from https en wikipedia org w index php title StAR related transfer domain amp oldid 1187749556, wikipedia, wiki, book, books, library,
