Protein transport systems transport up to 40% of proteins: 10% of B. subtilis proteins are secreted; 25-30% of proteins are membrane localized.
Protein transport systems are classified into multiple types. Each type recognizes a distinct signal peptide, and uses a distinct machinery to transport proteins into and through the membrane. Type I transport systems (eg. TolC) recognize N-terminal sequences, and transport unfolded proteins post-translationally. Type II transport systems (eg. Sec) recognize N-terminal positively charged sequences and transport nascent proteins co-translationally. Type III systems (eg. TAT) recognize C-terminal sequences and transport folded proteins.
M. genitalium possesses only a type II protein transport system. M. genitalium does not contain sortases or foldases.
M. genitalium Type II Sec System
M. genitalium possesses a type II protein transport system:
Signal recognition particle (SRP) – GTP-bound form competes with trigger factor which recognizes less hydrophobic sequences to binds signal peptides co-translationally. Coordinates nascent peptides to the signal particle receptor. Recognizes a positively charged N-terminal sequence of 10-15 residues. SRP is a ribonucleoprotein consisting of 1 protein subunit (Ffh, MG_048) which contains a GTP binding domain and 1 4.5S RNA (scRNA, ffs, MG_0001)
Signal recognition particle receptor (SR, FtsY, MG_297) – GTP-bound form binds signal recognition particle, thereby localizing the nascent peptide to the membrane. Hydrolysis of both GTPs bound to the receptor and to Ffh dissociates the peptide-SRP-SR complex, freeing the SRP, and shuttling a peptide-SR complex to the translocase [PUB_0010].
SecA translocase – Processively translocates the nascent polypeptide through the translocase pore via an ATP-dependent mechanism. SecA translocates 4-5 aa/ATP [PUB_0003] at a rate 270 pmol aa/min [PUB_0001].
SecYEGDF YjaC translocase pore – Forms a membrane pore through which unfolded proteins pass. Accessory proteins such as YjaC increase the efficiency of transport and are not essential. Integral membrane proteins begin folding by a phosphatidyl ethanolamine-dependent mechanism while translocating through the membrane. Membrane protein complexation occurs after membrane insertion.
Type II signal peptidase – Extracellularly cleaves the signal peptide of lipoproteins at a lipobox (L[ASI][GA]C).
Diacylglyceryl transferase – Transfers a N-terminal lipid anchor to lipoproteins after cleavage by the type II signal peptidase.
Note_ProteinLocalization_SignalPeptides describes the curation of protein signal peptides.
Translocates protein to and through membrane using
signal recognition particle
signal recognition particle receptor
Cleaves signal peptides of, and transfers diacylglyceryl to lipoproteins using
prolipoprotein signal peptidase II
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Eds Dalbey RE, von Heijne G. Protein Targeting, Transport, and Translocation. Academic Press, San Diego (2002). WholeCell: PUB_0003, ISBN: 9780122007316
Bernstein HD. The biogenesis and assembly of bacterial membrane proteins. Curr Opin Microbiol 3, 203-9 (2000). WholeCell: PUB_0635, PubMed: 10744997
Dowhan W, Bogdanov M. Lipid-dependent membrane protein topogenesis. Annu Rev Biochem 78, 515-40 (2009). WholeCell: PUB_0636, PubMed: 19489728
Hutchings MI, Palmer T, Harrington DJ, Sutcliffe IC. Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold 'em, knowing when to fold 'em. Trends Microbiol 17, 13-21 (2009). WholeCell: PUB_0629, PubMed: 19059780
Peluso P, Shan SO, Nock S, Herschlag D, Walter P. Role of SRP RNA in the GTPase cycles of Ffh and FtsY. Biochemistry 40, 15224-33 (2001). WholeCell: PUB_0010, PubMed: 11735405
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