Braun's lipoprotein
{{Infobox protein family
|Name=Lipoprotein leucine-zipper
|Pfam=PF04728
|Symbol=LPP
|InterPro=IPR006817
|below=Use {{InterPro|IPR016367|l=n}} for full protein. E. coli protein is {{UniProt|P69776}}.
|CATH=1jccA00
|SCOP=d1jcca_
}}
Braun's lipoprotein (BLP, Lpp, murein lipoprotein, or major outer membrane lipoprotein) was first identified by V. Braun and K. Rehn in 1969, it was the first Lipoprotein identified prompting much further study in this area.{{cite journal |last1=Braun |first1=Volkmar |title=Chemical characterization, spatial distribution and function of a lipoprotein (murein-lipoprotein) of the E. coli cell wall. The specific effect of trypsin on the membrane structure |journal=European Journal of Biochemistry |date=October 10, 1969 |volume=10 |issue=3 |pages=426–38 |doi=10.1111/j.1432-1033.1969.tb00707.x |pmid=4899922}} It is found in some gram-negative cell walls, is one of the most abundant membrane proteins; its molecular weight is about 7.2 kDa. It is bound at its C-terminal end (a lysine) by a covalent bond to the peptidoglycan layer (specifically to diaminopimelic acid molecules{{cite book |last1=Seltmann |first1=Guntram |first2=Otto |last2=Holst |year=2002 |title=The Bacterial Cell Wall |location=Berlin |publisher=Springer |pages=81–82 |isbn=3-540-42608-6 }}) and is embedded in the outer membrane by its hydrophobic head (a cysteine with lipids attached). BLP tightly links the two layers and provides structural integrity to the outer membrane.
Characteristics
The gene encoding Braun's lipoprotein initially produces a protein composed of 78 amino acids, which includes a 20 amino acid signal peptide at the amino terminus.{{cite journal |vauthors=Dramsi S, Magnet S, Davison S, Arthur M |title=Covalent attachment of proteins to peptidoglycan |journal=FEMS Microbiology Reviews |volume=32 |issue=2 |pages=307–20 |year=2008 |pmid=18266854 |doi=10.1111/j.1574-6976.2008.00102.x |doi-access=free }} The mature protein is 6 kDa in size.{{cite journal |vauthors=Konovalova A, Silhavy TJ |title=Outer membrane lipoprotein biogenesis: Lol is not the end |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=370 |issue=1679 |year=2015 |pmid=26370942 |doi=10.1098/rstb.2015.0030 |pmc=4632606 }} Three monomers of Lpp assemble into a leucine zipper coiled-coil trimer.{{cite journal |vauthors=Kovacs-Simon A, Titball RW, Michell SL |title=Lipoproteins of bacterial pathogens |journal=Infection and Immunity |volume=79 |issue=2 |pages=548–61 |year=2011 |pmid=20974828 |pmc=3028857 |doi=10.1128/IAI.00682-10 }}
Large amounts of Braun's lipoprotein is present, more than any other protein in E. coli.{{cite journal |vauthors=Silhavy TJ, Kahne D, Walker S |title=The bacterial cell envelope |journal=Cold Spring Harbor Perspectives in Biology |volume=2 |issue=5 |pages=a000414 |year=2010 |pmid=20452953 |pmc=2857177 |doi=10.1101/cshperspect.a000414 }} Unlike other lipoproteins, it is linked covalently to the peptidoglycan. Lpp connects the outer membrane to the peptidoglycan. Lpp is anchored to the outer membrane by its amino-terminal lipid group. In E. coli, one third of Lpp proteins form a peptide bond via the side chain of its carboxy-terminal lysine with diaminopimelic acid in the peptidoglycan layer.{{cite book|last1=Vollmer|first1=Waldemar|editor1-last=Ehrmann|editor1-first=Michael|title=The Periplasm|date=2007|publisher=ASM Press|location=Washington, DC|isbn=9781555813987|pages=198–213|edition=[Online-Ausg.].|chapter=Structure and biosynthesis of the murein (peptidoglycan) sacculus}} The rest of the Lpp molecules are present in a "free" form unlinked to peptidoglycan. The free form is exposed on the surface of E. coli.
Functions
Lpp, along with another OmpA-like lipoprotein called Pal/OprL ({{UniProt|P0A912}}), maintains the stability of the cell envelope by attaching the outer membrane to the cell wall.
Lpp has been proposed as a virulence factor of Yersinia pestis, the cause of plague.{{cite journal |vauthors=Butler T |title=Plague into the 21st century |journal=Clinical Infectious Diseases |volume=49 |issue=5 |pages=736–42 |year=2009 |pmid=19606935 |doi=10.1086/604718 |doi-access=free }} Y. pestis needs lpp for maximum survival in macrophages and to efficiently kill mouse models of bubonic and pneumonic plague.{{cite journal |vauthors=Smiley ST |title=Immune defense against pneumonic plague |journal=Immunological Reviews |volume=225 |pages=256–71 |year=2008 |pmid=18837787 |pmc=2804960 |doi=10.1111/j.1600-065X.2008.00674.x }}
Immunology
Braun's lipoprotein binds to the pattern recognition receptor TLR2. Lpp induces adhesion of neutrophils to human endothelial cells by activating the latter.{{cite journal |vauthors=McIntyre TM, Prescott SM, Weyrich AS, Zimmerman GA |title=Cell-cell interactions: leukocyte-endothelial interactions |journal=Current Opinion in Hematology |volume=10 |issue=2 |pages=150–8 |year=2003 |pmid=12579042 |doi= 10.1097/00062752-200303000-00009}}