Note_ProteinLocalization_SignalPeptides – ProteinLocalization_SignalPeptides

WID Note_ProteinLocalization_SignalPeptides
Name ProteinLocalization_SignalPeptides
Comments We assigned each protein monomer and complex to one of the localizations: Integral membrane (25-30% of bacterial proteins are localized to the membrane [PUB_0003]) Lipoprotein Cytoplasmic Extracellular (10% of B. subtilis proteins are secreted [PUB_0003]) Terminal oganelle, cytoplasmic Terminal organelle, integral membrane The localization of each protein, and the type II signal peptide length of lipoproteins was compiled from several sources: Computational prediction of membrane spanning domains and signal peptides Phobius [PUB_0262] PrediSi [PUB_0255] SignalP-HMM [PUB_0263] SignalP-NN [PUB_0263] SOSUI [PUB_0261, PUB_0264] SPdb database of observed signal peptides [PUB_0253] Mass-Spec determination of the N-terminal residue of each protein [PUB_0280] Databases of protein localization: BRENDA [PUB_0570], DBSubLoc [PUB_0573], EchoBase [PUB_0574], GenoBase [PUB_0386], PSortDB [PUB_0572], and UniProt [PUB_0096] Primary literature of the composition of the terminal organelle [PUB_0088, PUB_0091, PUB_0406, PUB_0407, PUB_0408, PUB_0409] Primary literature [PUB_0284, PUB_0303] Note M. genitalium does not contain a C-terminal signal sequence recognizing Tat protein transporter homolog. Additionally, we tried unsuccessfully to include computational predictions from these sources: SecretomeP – didn't predicted any secreted peptides [PUB_0252] LipPred – had CGI and bad request errors [PUB_0254] SIG-Pred – found no signal sequences [PUB_0255] sigcleave – unclear what it returns [PUB_0257] TatFind – identified no Tat signal peptides [PUB_0258] PilFind – identified no type IV pilin-like signal peptides [PUB_0259] SPEPLip – provides no easy way to query on genome-scale [PUB_0260] Terminal organelle localization was compiled from several experimental reports [PUB_0088, PUB_0089, PUB_0091, PUB_0092, PUB_0093]. Type II signal sequences are 10-15 amino acid long positively charged N-terminal sequences [PUB_0003]. These signal sequences are composed of three regions: n, h, and c. The n region is positively charged, and is 1-5 amino acids long. The h region is hydrophobic, is 7-15 amino acids in length, and forms an α-helix. The c region is slightly polor, is 3-7 amino acids in length, forms a βstrand, and is the most conserved. Lipoprotein type II signal sequences are cleaved at lipoboxes (L[ASI][GA]C) in the c region by signal peptidase II. Lipoproteins are anchored to the membrane outter leaflet by diacylglyceryls which are transferred to their N-terminal end by diacylglyceryl tranferase. Integral membrane proteins have 25 aa a-helical membrane spanning domains (except pores which have antiparallel ß-sheets) which anchor them to the membrane. Membrane signal sequences are not cleaved, and are generally longer than that of liproteins. Membrane protein translocation is mediated independent of translation by the ATP-dependent SecAY transporter [PUB_0003]. SecA transports with rate 270 pmol amino acid /min [PUB_0001] and energetic cost of 20-30 amino acids / ATP [PUB_0002]. SecA transport saturates at 0.1 uM peptide [PUB_0001]. Membrane proteins are shuttled to SecAY by chaperones (eg. GroEL, DnaK) [PUB_0003]. SecAY is assisted by several accessory factors (SecDEFG, YjaC) that improve the efficient of protein translocation [PUB_0003]. Lipoprotein and secretory protein translocation is mediated by SRP/FtsY and SecAY by a translation-dependent mechanism; (1) SRP competes with trigger fractor for nascent polypeptides and (2) SRP/FtsY shuttles the nascent polypeptide to the SecAY transporter [PUB_0003]. SRP is a GTP-dependent nucleoprotein composed of Ffh and the 4.5S scRNA [PUB_0003]. Membrane protein signal sequences generally anchor proteins to the membrane and are not cleaved [PUB_0003]. Liprotein and secretory protein signal sequences are cleaved on the extracellular side [PUB_0003]. Membrane spanning domains of integral membrane pores contain β-sheets [PUB_0003]. Most other membrane spanning domains contain hydrophobic α-helices approximately 25 amino acids in length [PUB_0003]. Membrane proteins are generally inserted linearly into the membrane, and fold inside the membrane beginning when the protein is partially inserted [PUB_0003, PUB_0636]. Integral membrane folding requires phosphatidylethanolamine (PE) [PUB_0636]; PE curvature stress increases lateral pressure on bilayer interior and decreases lateral pressue on bilayer exterior encouraging protein folding [PUB_0646]. phosphatidylglycerol (PG) is required for SecA insertion. Membrane protein complexation occurs following insertion [PUB_0018]. Lipoproteins are anchored in the outter leaflet by lipid modifications added after signal sequence cleavage [PUB_0629]. Often substrate binding subunits of ABC transporters are lipoproteins [PUB_0629]. Lipoproteins have several functions [PUB_0658]: Nutrient acquisition Adaptation Protein maturation Adherence Virulence Conjugation Sporulation Transport Signal transduction M. genitalium doesn't contain a Tat transporter, sortase [PUB_0631], or type I signal sequence protease [PUB_0634].
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Created 2012-10-01 15:07:34
Last updated 2012-10-01 15:13:58