Gene Symbol: glpG
Description: rhomboid intramembrane serine protease
Alias: ECK3410, JW5687
Species: Escherichia coli str. K-12 substr. MG1655
Products:     glpG

Top Publications

  1. Wu Z, Yan N, Feng L, Oberstein A, Yan H, Baker R, et al. Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat Struct Mol Biol. 2006;13:1084-91 pubmed
    ..Here we report the crystal structure of the transmembrane core domain of GlpG, a rhomboid-family intramembrane serine protease from Escherichia coli...
  2. Gallio M, Sturgill G, Rather P, Kylsten P. A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes. Proc Natl Acad Sci U S A. 2002;99:12208-13 pubmed
    ..This study provides the first evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell communication and that their biochemical properties could be more similar than previously anticipated...
  3. Urban S, Schlieper D, Freeman M. Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids. Curr Biol. 2002;12:1507-12 pubmed
    ..Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early. ..
  4. Wang Y, Zhang Y, Ha Y. Crystal structure of a rhomboid family intramembrane protease. Nature. 2006;444:179-80 pubmed
    Escherichia coli GlpG is an integral membrane protein that belongs to the widespread rhomboid protease family...
  5. Akiyama Y, Maegawa S. Sequence features of substrates required for cleavage by GlpG, an Escherichia coli rhomboid protease. Mol Microbiol. 2007;64:1028-37 pubmed
    ..We showed previously that GlpG, the Escherichia coli rhomboid, can cleave a type I model membrane protein Bla-LY2-MBP having the second ..
  6. Baker R, Young K, Feng L, Shi Y, Urban S. Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate. Proc Natl Acad Sci U S A. 2007;104:8257-62 pubmed
    ..Engineered mutants in the L1 loop and active-site region of the GlpG rhomboid protease suggest an important structural, rather than dynamic, gating function for the L1 loop that was ..
  7. Ben Shem A, Fass D, Bibi E. Structural basis for intramembrane proteolysis by rhomboid serine proteases. Proc Natl Acad Sci U S A. 2007;104:462-6 pubmed
    ..Our results reveal a mechanism to enable water-dependent catalysis at the depth of the hydrophobic milieu of the membrane and suggest how substrates gain access to the sequestered rhomboid active site. ..
  8. Urban S, Wolfe M. Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc Natl Acad Sci U S A. 2005;102:1883-8 pubmed
    ..This analysis promises to help reveal the biochemical mechanisms and biological roles of this most widely conserved membrane protein family. ..
  9. Bondar A, Del Val C, White S. Rhomboid protease dynamics and lipid interactions. Structure. 2009;17:395-405 pubmed publisher
    ..Several crystallographic structures of Escherichia coli GlpG rhomboid protease have been determined...

More Information


  1. Wang Y, Maegawa S, Akiyama Y, Ha Y. The role of L1 loop in the mechanism of rhomboid intramembrane protease GlpG. J Mol Biol. 2007;374:1104-13 pubmed
    ..Intramembrane proteases are important enzymes in biology. The recently solved crystal structures of rhomboid protease GlpG have provided useful insights into the mechanism of these membrane proteins...
  2. Dickey S, Baker R, Cho S, Urban S. Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity. Cell. 2013;155:1270-81 pubmed publisher
    ..These properties are unlike those of other studied proteases or membrane proteins but are strikingly reminiscent of one subset of DNA-repair enzymes, raising important mechanistic and drug-design implications. ..
  3. Koonin E, Makarova K, Rogozin I, Davidovic L, Letellier M, Pellegrini L. The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. Genome Biol. 2003;4:R19 pubmed
    ..This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular membrane proteases from membrane transporters is proposed. ..
  4. Lin E. Glycerol dissimilation and its regulation in bacteria. Annu Rev Microbiol. 1976;30:535-78 pubmed
  5. Wang Y, Ha Y. Open-cap conformation of intramembrane protease GlpG. Proc Natl Acad Sci U S A. 2007;104:2098-102 pubmed
    ..Previous crystallographic analysis of Escherichia coli GlpG, an intramembrane protease of the rhomboid family, has revealed an internal and hydrophilic active site in an ..
  6. Clemmer K, Sturgill G, Veenstra A, Rather P. Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii. J Bacteriol. 2006;188:3415-9 pubmed publisher
    ..stuartii aarA mutant serves as a useful host system to investigate rhomboid function. The Escherichia coli GlpG protein was shown to be functionally similar to AarA and rescued the above aarA-dependent phenotypes in P. stuartii...
  7. Erez E, Bibi E. Cleavage of a multispanning membrane protein by an intramembrane serine protease. Biochemistry. 2009;48:12314-22 pubmed publisher
    ..We utilized the Escherichia coli rhomboid GlpG, an intramembrane serine protease, and truncated versions of the E...
  8. Ha Y. Structural principles of intramembrane proteases. Curr Opin Struct Biol. 2007;17:405-11 pubmed
    ..methods, including the first report of an intramembrane protease crystal structure, that of Escherichia coli GlpG. Taken together, these studies started to reveal patterns of how intramembrane proteases are constructed, how ..
  9. Schweizer H, Sweet G, Larson T. Physical and genetic structure of the glpD-malT interval of the Escherichia coli K-12 chromosome. Identification of two new structural genes of the glp-regulon. Mol Gen Genet. 1986;202:488-92 pubmed
    ..In addition, two new structural genes of the glp regulon (glpE and glpG) located between the glpD and glpR genes were identified...
  10. Freeman M. Structural biology: enzyme theory holds water. Nature. 2006;444:153-5 pubmed
  11. Maegawa S, Ito K, Akiyama Y. Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli cytoplasmic membrane. Biochemistry. 2005;44:13543-52 pubmed
    We characterized Escherichia coli GlpG as a membrane-embedded protease and a possible player in the regulated intramembrane proteolysis in this organism...
  12. Ahmer B. Cell-to-cell signalling in Escherichia coli and Salmonella enterica. Mol Microbiol. 2004;52:933-45 pubmed
    ..The latter system has homologues in E. coli and Salmonella, as well as other bacteria, plants and animals. In fact, the protease components from Providencia and Drosophila are functionally interchangeable. ..
  13. Lazareno Saez C, Arutyunova E, Coquelle N, Lemieux M. Domain swapping in the cytoplasmic domain of the Escherichia coli rhomboid protease. J Mol Biol. 2013;425:1127-42 pubmed publisher
    Rhomboids are membrane-embedded serine proteases that cleave membrane protein substrates. Escherichia coli rhomboid GlpG (ecGlpG) consists of an N-terminal cytoplasmic domain and a membrane domain containing the active site...
  14. Paslawski W, Lillelund O, Kristensen J, Schafer N, Baker R, Urban S, et al. Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops. Proc Natl Acad Sci U S A. 2015;112:7978-83 pubmed publisher
    ..experiments on 69 mutants (engineered every 2-3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli...
  15. Foo A, Harvey B, Metz J, Goto N. Influence of hydrophobic mismatch on the catalytic activity of Escherichia coli GlpG rhomboid protease. Protein Sci. 2015;24:464-73 pubmed publisher
    ..High-resolution structures of the catalytic transmembrane domain of the Escherichia coli GlpG rhomboid have provided numerous insights that help explain how hydrolytic cleavage can be achieved below the ..
  16. Russell C, Richards A, Chang A, Mulvey M. The Rhomboid Protease GlpG Promotes the Persistence of Extraintestinal Pathogenic Escherichia coli within the Gut. Infect Immun. 2017;85: pubmed publisher
    ..One of the identified mucus-specific fitness genes encodes the rhomboid protease GlpG. In vitro, we found that the disruption of glpG had polar effects on the downstream gene glpR, ..
  17. Maegawa S, Koide K, Ito K, Akiyama Y. The intramembrane active site of GlpG, an E. coli rhomboid protease, is accessible to water and hydrolyses an extramembrane peptide bond of substrates. Mol Microbiol. 2007;64:435-47 pubmed
    Escherichia coli GlpG is an orthologue of the rhomboid proteases that catalyse intramembrane proteolysis of specific membrane proteins...
  18. Lemberg M, Menendez J, Misik A, Garcia M, Koth C, Freeman M. Mechanism of intramembrane proteolysis investigated with purified rhomboid proteases. EMBO J. 2005;24:464-72 pubmed
    ..We identify a motif shared between rhomboids and the recently discovered derlins, which participate in translocation of misfolded membrane proteins. ..
  19. Choi Y, Kawase S, Nishida T, Sakai H, Komano T, Kawamukai M, et al. Nucleotide sequence of the glpR gene encoding the repressor for the glycerol-3-phosphate regulon of Escherichia coli K12. Nucleic Acids Res. 1988;16:7732 pubmed
  20. Choi Y, Kawase S, Kawamukai M, Sakai H, Komano T. Regulation of glpD and glpE gene expression by a cyclic AMP-cAMP receptor protein (cAMP-CRP) complex in Escherichia coli. Biochim Biophys Acta. 1991;1088:31-5 pubmed
    ..These results indicate that the single CRP-binding site is a cis-acting element involved in the positive regulation of the expression of both glpD and glpE at the transcriptional level. ..
  21. Urban S, Baker R. In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells. Biol Chem. 2008;389:1107-15 pubmed publisher
    ..Using Escherichia coli rhomboid (GlpG) structures as a guide, we previously took a mutational approach to identify the GlpG gating mechanism that allows ..
  22. Ha Y, Akiyama Y, Xue Y. Structure and mechanism of rhomboid protease. J Biol Chem. 2013;288:15430-6 pubmed publisher
    ..Recent progress in crystallographic analysis of the Escherichia coli rhomboid protease GlpG in complex with inhibitors has provided new insights into the catalytic mechanism of the protease and its ..
  23. Yang B, Larson T. Multiple promoters are responsible for transcription of the glpEGR operon of Escherichia coli K-12. Biochim Biophys Acta. 1998;1396:114-26 pubmed
    ..a promoter located upstream of the glpE start codon, three internal glpGR promoters were identified that express glpG and/or glpR (glp repressor)...
  24. Schafer N, Truong H, Otzen D, Lindorff Larsen K, Wolynes P. Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease. Proc Natl Acad Sci U S A. 2016;113:2098-103 pubmed publisher
    We investigate the folding of GlpG, an intramembrane protease, using perfectly funneled structure-based models that implicitly account for the absence or presence of the membrane...
  25. Zoll S, Stanchev S, Began J, Skerle J, Lepšík M, Peclinovská L, et al. Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures. EMBO J. 2014;33:2408-21 pubmed publisher
    ..novel peptidyl-chloromethylketone (CMK) inhibitors and analysed their interactions with Escherichia coli rhomboid GlpG enzymologically and structurally...
  26. Zeng G, Ye S, Larson T. Repressor for the sn-glycerol 3-phosphate regulon of Escherichia coli K-12: primary structure and identification of the DNA-binding domain. J Bacteriol. 1996;178:7080-9 pubmed
    ..The glpE gene encodes an acidic, cytoplasmic protein of 108 amino acids with a molecular weight of 12,082. The glpG gene encodes a basic, cytoplasmic membrane-associated protein of 276 amino acids with a molecular weight of 31,278...
  27. Arutyunova E, Panigrahi R, Strisovsky K, Lemieux M. Production of Recombinant Rhomboid Proteases. Methods Enzymol. 2017;584:255-278 pubmed publisher
    ..The provided protocol yields 1-2.5mg of rhomboid enzyme per liter of bacterial culture and can assist in structural and functional studies of intramembrane proteases. ..