The LptA Protein of Escherichia coli Is a Periplasmic Lipid A-binding Protein Involved in the Lipopolysaccharide Export Pathway

The LptA protein of Escherichia coli has been implicated in the transport of lipopolysaccharide (LPS) from the inner membrane to the outer membrane. Here we provide evidence that LptA binds structurally diverse LPS substrates in vitro and demonstrate that it interacts specifically with the lipid A domain of LPS. These results are consistent with LptA playing a chaperone role in the transport of LPS across the periplasm and have implications for possible assembly models. The LptA protein of Escherichia coli has been implicated in the transport of lipopolysaccharide (LPS) from the inner membrane to the outer membrane. Here we provide evidence that LptA binds structurally diverse LPS substrates in vitro and demonstrate that it interacts specifically with the lipid A domain of LPS. These results are consistent with LptA playing a chaperone role in the transport of LPS across the periplasm and have implications for possible assembly models. Lipopolysaccharide (LPS) 2The abbreviations used are: LPS, lipopolysaccharide; Kdo, 3-deoxy-d-manno-octulosonic acid; PtdEtn, phosphatidylethanolamine; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight; OM, outer membrane; IM, inner membrane; R-LPS, rough LPS; S-LPS, smooth LPS; ABC, ATP-binding cassette; Ni-NTA, nickel-nitrilotriacetic acid; TLC, thin layer chromatography; O-PS, O-antigenic polysaccharide. 2The abbreviations used are: LPS, lipopolysaccharide; Kdo, 3-deoxy-d-manno-octulosonic acid; PtdEtn, phosphatidylethanolamine; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight; OM, outer membrane; IM, inner membrane; R-LPS, rough LPS; S-LPS, smooth LPS; ABC, ATP-binding cassette; Ni-NTA, nickel-nitrilotriacetic acid; TLC, thin layer chromatography; O-PS, O-antigenic polysaccharide. is a major component of the outer leaflet of the outer membrane (OM) of Gram-negative bacteria (1Nikaido H. Microbiol. Mol. Biol. Rev. 2003; 67: 593-656Crossref PubMed Scopus (2837) Google Scholar, 2Raetz C.R. Whitfield C. Annu. Rev. Biochem. 2002; 71: 635-700Crossref PubMed Scopus (3356) Google Scholar, 3Trent M.S. Stead C.M. Tran A.X. Hankins J.V. J. Endotoxin Res. 2006; 12: 205-223Crossref PubMed Scopus (268) Google Scholar). Lipid A (Fig. 1A) functions as the hydrophobic membrane anchor of LPS and is linked via a core oligosaccharide to the long chain polysaccharide known as O-antigen (2Raetz C.R. Whitfield C. Annu. Rev. Biochem. 2002; 71: 635-700Crossref PubMed Scopus (3356) Google Scholar). Two distinct pathways are involved in the biosynthesis of the lipid A-core and O-antigen (Fig. 2). The lipid A-core portion (known as “rough” LPS (R-LPS)) is synthesized by a conserved pathway involving proteins on the cytoplasmic surface of the inner membrane (IM) and is then transported across the IM by an essential ATP-binding cassette (ABC) transporter, MsbA (reviewed in Refs. 2Raetz C.R. Whitfield C. Annu. Rev. Biochem. 2002; 71: 635-700Crossref PubMed Scopus (3356) Google Scholar, 3Trent M.S. Stead C.M. Tran A.X. Hankins J.V. J. Endotoxin Res. 2006; 12: 205-223Crossref PubMed Scopus (268) Google Scholar, 4Polissi A. Georgopoulos C. Mol. Microbiol. 1996; 20: 1221-1233Crossref PubMed Scopus (109) Google Scholar, 5Doerrler W.T. Raetz C.R. J. Biol. Chem. 2002; 277: 36697-36705Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, 6Raetz C.R. Reynolds C.M. Trent M.S. Bishop R.E. Annu. Rev. Biochem. 2007; 76: 295-329Crossref PubMed Scopus (923) Google Scholar). An additional protein, YhjD, has recently been implicated in LPS export across the IM (7Mamat U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar). Hence, this process is more complicated than initially thought. O-antigen is synthesized separately and is present in its completed form at the periplasmic face of the IM, attached to the carrier lipid (undecaprenyl diphosphate). These two major pathways converge with the ligation of O-antigen to lipid A-core at the periplasmic face of the IM, mediated by an integral membrane protein, WaaL (reviewed in Ref. 2Raetz C.R. Whitfield C. Annu. Rev. Biochem. 2002; 71: 635-700Crossref PubMed Scopus (3356) Google Scholar). This generates “smooth” LPS (S-LPS). Finally, the completed LPS molecule is translocated to the cell surface. O-antigen attachment is not required for lipid A-core transport to the OM because there is heterogeneity in the LPS molecular species; both R-LPS and S-LPS are found on the cell surface. The smallest LPS derivative supporting viability in Escherichia coli is lipid IVA (7Mamat U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar, 8Meredith T.C. Aggarwal P. Mamat U. Lindner B. Woodard R.W. ACS Chem. Biol. 2006; 1: 33-42Crossref PubMed Scopus (114) Google Scholar) (Fig. 1B). However, this requires mutations in either MsbA or the integral membrane protein of unknown function, YhjD, to suppress the normally lethal consequence of an incomplete lipid A (7Mamat U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar).FIGURE 2Overview of LPS biosynthesis. The lipid A-core domain is synthesized at the cytoplasmic face of the inner membrane and is exported to the periplasm by MsbA, an ABC transporter. The O polysaccharide is assembled separately on a lipid carrier (undecaprenyl diphosphate) and is presented for ligation to the lipid A-core by WaaL in the periplasm (reviewed in Refs. 2Raetz C.R. Whitfield C. Annu. Rev. Biochem. 2002; 71: 635-700Crossref PubMed Scopus (3356) Google Scholar and 6Raetz C.R. Reynolds C.M. Trent M.S. Bishop R.E. Annu. Rev. Biochem. 2007; 76: 295-329Crossref PubMed Scopus (923) Google Scholar). The completed LPS molecules and the R-LPS are transported to the cell surface by the same pathway, involving several essential proteins whose mechanism of action is unresolved. Nomenclature in parentheses refers to historical gene/protein names; the Lpt designations are more recent. OS, oligosaccharide.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Although the early phases of LPS biosynthesis are generally well known, the mechanisms of LPS transport and its insertion into the OM still remain unclear. Equally unknown is the extent of coordination and interplay with other trafficking events required for OM assembly (9Bos M.P. Robert V. Tommassen J. Annu. Rev. Microbiol. 2007; 61: 191-214Crossref PubMed Scopus (352) Google Scholar, 10Ruiz N. Kahne D. Silhavy T.J. Nat. Rev. Microbiol. 2006; 4: 57-66Crossref PubMed Scopus (344) Google Scholar). Recent studies have begun to shed light on the essential components of LPS transport. These include the conserved OM protein known as LptD (formerly Imp or OstA). LptD is essential in E. coli, and depletion of this protein results in abnormalities in OM assembly and increased OM density (evident in sucrose gradient centrifugation profiles), which are consistent with reduced lipid incorporation (11Wu T. Malinverni J. Ruiz N. Kim S. Silhavy T.J. Kahne D. Cell. 2005; 121: 235-245Abstract Full Text Full Text PDF PubMed Scopus (556) Google Scholar, 12Braun M. Silhavy T.J. Mol. Microbiol. 2002; 45: 1289-1302Crossref PubMed Scopus (193) Google Scholar). LptD exists in a complex with LptE (formerly RlpB), an essential OM lipoprotein, the absence of which results in a phenotype resembling an LptD defect (13Wu T. McCandlish A.C. Gronenberg L.S. Chng S.S. Silhavy T.J. Kahne D. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 11754-11759Crossref PubMed Scopus (267) Google Scholar). These proteins may provide a mechanism to move the LPS molecules into and/or across the OM barrier. Recently, five additional essential E. coli proteins (LptA, LptB, LptC (formerly YrbK), LptF (formerly YjgP), and LptG (formerly YjgQ)) have been implicated in LPS transport to the OM (14Sperandeo P. Pozzi C. Deho G. Polissi A. Res. Microbiol. 2006; 157: 547-558Crossref PubMed Scopus (72) Google Scholar, 15Sperandeo P. Cescutti R. Villa R. Di Benedetto C. Candia D. Deho G. Polissi A. J. Bacteriol. 2007; 189: 244-253Crossref PubMed Scopus (176) Google Scholar, 16Sperandeo, P., Lau, F. K., Carpentieri, A., De Castro, C., Molinaro, A., Deho, G., Silhavy, T. J., and Polissi, A. (2008) J. Bacteriol., in pressGoogle Scholar, 17Ruiz N. Gronenberg L.S. Kahne D. Silhavy T.J. Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 5537-5542Crossref PubMed Scopus (194) Google Scholar). LptB is a cytoplasmic nucleotide-binding domain protein belonging to the ABC protein superfamily (15Sperandeo P. Cescutti R. Villa R. Di Benedetto C. Candia D. Deho G. Polissi A. J. Bacteriol. 2007; 189: 244-253Crossref PubMed Scopus (176) Google Scholar). LptF and LptG have been proposed as transmembrane domain proteins that participate with LptB in an ABC protein complex to extract LPS from the IM en route to the OM (17Ruiz N. Gronenberg L.S. Kahne D. Silhavy T.J. Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 5537-5542Crossref PubMed Scopus (194) Google Scholar). LptC is a bitopic IM protein that has also been suggested to play a role in LPS extraction from the IM (14Sperandeo P. Pozzi C. Deho G. Polissi A. Res. Microbiol. 2006; 157: 547-558Crossref PubMed Scopus (72) Google Scholar, 15Sperandeo P. Cescutti R. Villa R. Di Benedetto C. Candia D. Deho G. Polissi A. J. Bacteriol. 2007; 189: 244-253Crossref PubMed Scopus (176) Google Scholar, 16Sperandeo, P., Lau, F. K., Carpentieri, A., De Castro, C., Molinaro, A., Deho, G., Silhavy, T. J., and Polissi, A. (2008) J. Bacteriol., in pressGoogle Scholar). LptA, the subject of this investigation, is proposed to be a periplasmic protein (15Sperandeo P. Cescutti R. Villa R. Di Benedetto C. Candia D. Deho G. Polissi A. J. Bacteriol. 2007; 189: 244-253Crossref PubMed Scopus (176) Google Scholar). There are apparent similarities to the Lol proteins involved in export of OM lipoproteins. LolCDE is an ABC protein pump that releases nascent lipoproteins to a periplasmic chaperone, LolA (18Taniguchi N. Tokuda H. J. Biol. Chem. 2008; 283: 8538-8544Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). LolA transfers its cargo to LolB in the OM (19Taniguchi N. Matsuyama S. Tokuda H. J. Biol. Chem. 2005; 280: 34481-34488Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar). In a comparable LPS scenario, LptBFG (and perhaps LptC) might release LPS molecules from the biosynthesis/ligation site in the IM into the translocation pathway. LptA is a candidate for the chaperone delivering nascent LPS molecules to LptDE in the OM. However, attempts to demonstrate LPS release in spheroplasts have been unsuccessful, despite using conditions where efficient lipoprotein release was detected (20Tefsen B. Geurtsen J. Beckers F. Tommassen J. de Cock H. J. Biol. Chem. 2005; 280: 4504-4509Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). In an alternative translocation pathway, LPS molecules may be translocated to the OM via sites where the IM and OM come into apposition (20Tefsen B. Geurtsen J. Beckers F. Tommassen J. de Cock H. J. Biol. Chem. 2005; 280: 4504-4509Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 21Muhlradt P.F. Menzel J. Golecki J.R. Speth V. Eur. J. Biochem. 1973; 35: 471-481Crossref PubMed Scopus (101) Google Scholar). A molecular scaffold approach is involved in the translocation of capsular polysaccharides in E. coli (22Collins R.F. Beis K. Dong C. Botting C.H. McDonnell C. Ford R.C. Clarke B.R. Whitfield C. Naismith J.H. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: 2390-2395Crossref PubMed Scopus (122) Google Scholar). Resolution of these possibilities requires insight from biochemical information for the translocation components, which is currently lacking. Because LptA was implicated in the transport of LPS to the OM, we investigated its ability to bind to LPS. Using a variety of LPS substrates, we now report that LptA specifically binds to the lipid A domain of LPS and also is capable of binding to the lipid A precursor lipid IVA. To our knowledge, these are the first functional data for any of the OM or periplasmic components of the LPS export apparatus. Recombinant DNA Techniques—Plasmids, PCR amplification products, and DNA fragments were isolated using the Qiagen Spin Prep, Qiaquick PCR Purification, and Qiaquick were from PCR were from DNA and were from and used to the was by with from and J. J. Microbiol. PubMed Scopus Google Scholar). DNA was using the to the of the was from E. coli DNA with and The the a The PCR was with the and and into the sites of a an for D. J. J. Bacteriol. PubMed Scopus Google to the The of the was by DNA and of coli the was at in J. Bacteriol. PubMed Google Scholar) and for This was in and the density of the of was for by to a of were then by centrifugation at for The cell was in A and and the were by a and were by centrifugation for The membrane was from the by for The protein was then from the using The was with A and The protein was in A by a with A were by by PubMed Scopus Google Scholar). The were using a and in and The protein was using a molecular of protein were from of was by the Biochem. PubMed Scopus Google using as the of molecular of was by at the of The of LptA was on a with B. was at a of The was with molecular were with a of of in a of of of E. coli were and as and were as M.S. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). were at and in at The and membrane were in by at for and then on were by or by proteins were and with Qiagen to the was used with a to and with and LPS from E. coli was isolated using the O. K. Chem. Scholar). R-LPS from E. coli was isolated using the C. O. O. Eur. J. Biochem. PubMed Scopus Google Scholar). of Lipid A and Lipid A lipid A precursor IVA was from of and the lipid using the present in of E. coli as M.S. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S.S. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). IVA was by E. coli the as S.S. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Raetz C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). A was from IVA by with carrier protein and and as C.M. Raetz C.R. J. Biol. Chem. 2005; 280: Full Text Full Text PDF PubMed Scopus Google Scholar, T. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, T. Raetz C.R. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). the were the were isolated as S.S. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In LPS in vitro LPS binding was on the approach M.S. Whitfield C. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: PubMed Scopus Google Scholar) with the were in in of and either LPS or of lipid A or at a of was at for on a in of was to the and for the was to the and the was The was then with of was with of and the was more A with of was to protein was The in the lipid A binding was detected by In from was thin layer and the were a for IVA was as the binding the lipid was using the and binding either IVA or A as the binding the were in the and and of the to a the was detected and using a with In was in and to a where the was The were in by for in a to with at for on a in of was to the and for the was to the and as A of of were and in of of from the were a was using and was detected by the with in and then LPS was by using from and by C.M. Biochem. PubMed Scopus Google to the and LptA a by (15Sperandeo P. Cescutti R. Villa R. Di Benedetto C. Candia D. Deho G. Polissi A. J. Bacteriol. 2007; 189: 244-253Crossref PubMed Scopus (176) Google Scholar) proposed that LptA is a periplasmic protein with a molecular of and that its is the of a of E. coli LptA using the E. A. C. A. Res. 2003; PubMed Scopus Google Scholar) a the protein is exported into the In the LptA in was recently to be in the membrane than in the periplasmic (9Bos M.P. Robert V. Tommassen J. Annu. Rev. Microbiol. 2007; 61: 191-214Crossref PubMed Scopus (352) Google Scholar). to the possible membrane of LptA from E. coli, we a of LptA the of the the (Fig. the and membrane were with two centrifugation on the from the is to the (Fig. and a of was in the membrane (Fig. and and this was with the increased of an was to by and its was by with (Fig. and of the of two protein of apparent molecular However, of the same protein major at to a protein that at the molecular E. A. C. A. Res. 2003; PubMed Scopus Google This is consistent with the transport of a periplasmic protein across the that is a not The additional protein in the to be a form of with A was for an O-antigenic polysaccharide domain protein M.S. Whitfield C. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: PubMed Scopus Google Scholar). not LptA also has These results and the that E. coli LptA is a periplasmic protein (15Sperandeo P. Cescutti R. Villa R. Di Benedetto C. Candia D. Deho G. Polissi A. J. Bacteriol. 2007; 189: 244-253Crossref PubMed Scopus (176) Google Scholar). LptA to LPS and R-LPS In to the Lol role of LptA is a periplasmic chaperone To LptA with LPS LPS from E. coli was with The protein was then from the by and for the of LPS. M.S. Whitfield C. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: PubMed Scopus Google LPS not bind to (Fig. and the a of R-LPS and S-LPS is in the In the of a of LPS is and with (Fig. LPS binding with proteins not LptA also binds S-LPS from other not that the of the role in E. coli not to mutations in the biosynthesis D. PubMed Scopus Google Scholar). in LptA also binds R-LPS from evidence that the is not required for LptA to Lipid we to the core oligosaccharide domain of LPS was required for In to the core oligosaccharide domain is for the A (Fig. 1A) was synthesized in vitro and to the same binding In the absence of the of the lipid was detected in the (Fig. However, with the of lipid A with the protein These results that the outer core oligosaccharide domain is not required in the binding of LPS by LptA (Fig. In we IVA and IVA in These the two attached to the at the and (Fig. 1B). were by (Fig. and that of the lipid A and the and of of lipid A are not essential for the of these LPS LptA to bind to the lipid A domain of LPS, and efficient binding be in vitro with as as LptA to the E. coli, the OM is C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). are synthesized at the cytoplasmic of the IM and are transported across the IM by an unknown mechanism in to the OM Annu. Rev. Microbiol. 2003; PubMed Scopus Google Scholar). MsbA has been implicated in the of both LPS and across the IM W.T. Mol. Microbiol. 2006; PubMed Scopus Google this is still (7Mamat U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar, B. M.P. Beckers F. Tommassen J. de Cock H. J. Biol. Chem. 2005; 280: Full Text Full Text PDF PubMed Scopus Google Scholar). (20Tefsen B. Geurtsen J. Beckers F. Tommassen J. de Cock H. J. Biol. Chem. 2005; 280: 4504-4509Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar) that synthesized were not transported to the OM of that a periplasmic to LolA may be we to LptA also bind to E. coli was in the binding with not bind to not and with it was detected in the (Fig. was also used in an to as an of LPS binding to was not The that of the of MsbA, LptA is of a periplasmic for lipid LPS and are essential components of the OM in Gram-negative and and biosynthesis are well known (2Raetz C.R. Whitfield C. Annu. Rev. Biochem. 2002; 71: 635-700Crossref PubMed Scopus (3356) Google Scholar, U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar, Annu. Rev. Microbiol. 2003; PubMed Scopus Google Scholar). However, is known the mechanisms of transport and assembly of both of these in the OM (9Bos M.P. Robert V. Tommassen J. Annu. Rev. Microbiol. 2007; 61: 191-214Crossref PubMed Scopus (352) Google Scholar, 10Ruiz N. Kahne D. Silhavy T.J. Nat. Rev. Microbiol. 2006; 4: 57-66Crossref PubMed Scopus (344) Google Scholar). and of the inner membrane protein MsbA has insight into the LPS is transported across the IM W.T. Raetz C.R. J. Biol. Chem. 2002; 277: 36697-36705Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar, W.T. Raetz C.R. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). However, it is still LPS is transported across the periplasm and into the OM. The data that LptA functions as an binding to lipid LptA may the hydrophobic LPS in the of the This is to the Lol for lipoprotein transport (9Bos M.P. Robert V. Tommassen J. Annu. Rev. Microbiol. 2007; 61: 191-214Crossref PubMed Scopus (352) Google Scholar). LolA a with an and a hydrophobic of that the of the lipoprotein H. Matsuyama S. PubMed Scopus Google Scholar). for LptA that this protein also B. C. J. Mol. Biol. PubMed Scopus Google and it is that LptA may with are from LolA to the outer membrane in an process (19Taniguchi N. Matsuyama S. Tokuda H. J. Biol. Chem. 2005; 280: 34481-34488Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar). LolB with The that LptA to the conserved periplasmic domain of LptD PubMed Scopus Google Scholar, B. Res. PubMed Scopus Google Scholar) is the that a (20Tefsen B. Geurtsen J. Beckers F. Tommassen J. de Cock H. J. Biol. Chem. 2005; 280: 4504-4509Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar) was to LPS release from other to the Lol for lipoprotein export and assembly into the OM. studies that LPS be transported to the OM by of the IM and the OM. for this from studies with where synthesized LPS molecules at sites IM and OM P.F. Menzel J. Golecki J.R. Speth V. Eur. J. Biochem. 1973; 35: 471-481Crossref PubMed Scopus (101) Google Scholar). These sites have been to as J. Microbiol. PubMed Scopus Google Scholar) has been as was to the used for E. Mol. Microbiol. 4: PubMed Scopus Google Scholar, J. Biol. PubMed Scopus Google Scholar). However, it is now that the in and M. G. in pressGoogle J. E. C. V. Biol. PubMed Scopus (122) Google and V. J. C. Annu. Rev. Biochem. PubMed Scopus Google H. 2006; PubMed Scopus Google and K. V. S. E. Annu. Rev. Microbiol. 2005; PubMed Scopus Google Scholar) protein N. Annu. Rev. Biochem. 2008; PubMed Scopus Google Scholar) and export (22Collins R.F. Beis K. Dong C. Botting C.H. McDonnell C. Ford R.C. Clarke B.R. Whitfield C. Naismith J.H. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: 2390-2395Crossref PubMed Scopus (122) Google Scholar). studies have the that the insertion sites are not a J. Bacteriol. 2005; PubMed Scopus Google Scholar). The of a periplasmic protein not additional components in a molecular scaffold the periplasm it sites of as these be by the and of the outer membrane components LptD and is well that Gram-negative bacteria export LPS molecules with diverse and to the outer membrane; these are in LPS by Meredith T.C. Aggarwal P. Mamat U. Lindner B. Woodard R.W. ACS Chem. Biol. 2006; 1: 33-42Crossref PubMed Scopus (114) Google Scholar) recently a E. coli with an outer membrane of lipid an LPS derivative that both This is and exported across the IM (7Mamat U. Meredith T.C. Aggarwal P. Kuhl A. Kirchhoff P. Lindner B. Hanuszkiewicz A. Sun J. Holst O. Woodard R.W. Mol. Microbiol. 2008; 67: 633-648Crossref PubMed Scopus (39) Google Scholar, 8Meredith T.C. Aggarwal P. Mamat U. Lindner B. Woodard R.W. ACS Chem. Biol. 2006; 1: 33-42Crossref PubMed Scopus (114) Google Scholar). An essential for any periplasmic export component the ability to diverse LPS the essential LPS LptA In that LptA are in Gram-negative of a conserved pathway. The essential for LptA for its conserved and its periplasmic LptA an candidate for the of Gram-negative in this was in the of LptA was The in a the mechanism by which LptA binds LPS and in its export is not by the M. P., G., Polissi, A., and (2008) J. Mol. Biol.

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