Disease relevance of lspA

• In genetic complementation, recombinant lspA from R. typhi significantly restores the growth of temperature-sensitive E. coli Y815 at the nonpermissive temperature, supporting its biological activity as SPase II in prolipoprotein processing [1].
• The lspA Gene, Encoding the Type II Signal Peptidase of Rickettsia typhi: Transcriptional and Functional Analysis [1].
• Here, we describe the analysis of lspA, encoding a putative SPase II, an essential component of lipoprotein processing in gram-negative bacteria, from Rickettsia typhi [1].
• In contrast, SPase II is not essential for growth and viability of the Gram-positive eubacterium Bacillus subtilis [2].
• To explore further the importance of lipoprotein processing in Gram-positive eubacteria, an SPase II mutant strain of Lactococcus lactis was constructed [2].

High impact information on lspA

• Here we experimentally verify this prediction by metabolic labeling of subunit b with [14C]palmitic acid and by in vivo interfering with the processing of the prolipoprotein form of subunit b by the antibiotic globomycin, a specific inhibitor of the signal peptidase II [3].
• This new cleavage between alanine and lysine residues was resistant to globomycin, a specific inhibitor for signal peptidase II [4].
• Both non-mutant and mutant signal peptides appeared to be removed at the same unique site between cysteine 21 and serine 22, one residue from the E. coli signal peptidase II processing site [5].
• Sequence analysis of the pG gene revealed an open reading frame encoding a putative lipoprotein of 196 amino acids with a calculated molecular mass of 22 kDa and a consensus cleavage sequence (Leu-X-Y-Z-Cys) recognized by signal peptidase II [6].
• DNA and amino acid sequence analyses indicated an open reading frame encoding 403 amino acids, with the first 25 amino acids corresponding to a leader peptide terminated by a signal peptidase II processing site of Val-Val-Gly-Cys [7].

Chemical compound and disease context of lspA

• Overexpression of R. typhi lspA in Escherichia coli confers increased globomycin resistance, indicating its function as SPase II [1].
• Globomycin, an inhibitor of lipoprotein-specific signal peptidase II, was lethal for E. coli only when Lpp possessed the C-terminal lysine [8].
• In partition chromatography the recMPT83 partitioned in the water phase while 26 kDa MPB83 in BCG culture filtrate partitioned in the lipid phase confirming that lipidation at the N-terminal cysteine residue occurs after the splitting of the polypeptide chain by signal peptidase II [9].

Biological context of lspA

• The higher transcriptional level of all three genes at the preinfection time point indicates that only live and metabolically active rickettsiae are capable of infection and inducing host cell phagocytosis. lspA and lgt, which are involved in lipoprotein processing, show similar levels of expression [1].
• Unmodified prolipoprotein with the putative consensus sequence undergoes sequential modification and processing reactions catalyzed by glyceryl transferase, O-acyl transferase(s), prolipoprotein signal peptidase (signal peptidase II), and N-acyl transferase to form mature lipoprotein [10].
• Analysis of the amino acid sequence derived from the DNA sequence of the P67 gene revealed a typical prokaryotic signal peptidase II membrane lipoprotein lipid attachment site and a transmembrane structure domain in the leader sequence at the amino-terminal end of the protein [11].
• Signal sequence processing of LppC synthesized in the homologous host or expressed from plasmid pLPP2 in Escherichia coli was sensitive to globomycin, a selective inhibitor of lipoprotein-specific signal peptidase II [12].

Anatomical context of lspA

• The inverted plasma membrane vesicles used here must therefore contain active lipid-modifying enzymes and signal peptidase II [13].

Other interactions of lspA

• The transcription of lspA, lgt (encoding prolipoprotein transferase), and lepB (encoding type I signal peptidase), monitored by real-time quantitative reverse transcription-PCR, reveals a differential expression pattern during various stages of rickettsial intracellular growth [1].

References