Bam A

{{Short description|Outer membrane protein}} {{Infobox protein family | Symbol = BamA | Name = OMP insertion (BamComplex) porin | image = | width = | caption = | InterPro= IPR023707 | SMART= | PROSITE = | SCOP = | TCDB = 1.B.33 | OPM family= 179 | OPM protein= 5ayw | Pfam= PF01103 | PDB= | Membranome superfamily= }} '''BamA''' is a β-barrel, outer membrane protein found in Gram-negative bacteria and it is the main and vital component of the '''β-barrel assembly machinery''' (BAM) complex in those bacteria.<ref name="pmid19399587">{{cite journal | vauthors = Walther DM, Rapaport D, Tommassen J | title = Biogenesis of beta-barrel membrane proteins in bacteria and eukaryotes: evolutionary conservation and divergence | journal = Cellular and Molecular Life Sciences | volume = 66 | issue = 17 | pages = 2789–804 | date = September 2009 | pmid = 19399587 | pmc = 2724633 | doi = 10.1007/s00018-009-0029-z }}</ref> BAM Complex consists of five components; BamB, BamC, BamD, BamE (all are lipoproteins) and BamA (Outer membrane protein).<ref name="pmid17190789">{{cite journal | vauthors = Habib SJ, Waizenegger T, Niewienda A, Paschen SA, Neupert W, Rapaport D | title = The N-terminal domain of Tob55 has a receptor-like function in the biogenesis of mitochondrial beta-barrel proteins | journal = The Journal of Cell Biology | volume = 176 | issue = 1 | pages = 77–88 | date = January 2007 | pmid = 17190789 | pmc = 2063629 | doi = 10.1083/jcb.200602050 }}</ref><ref name="pmid19182809">{{cite journal | vauthors = Knowles TJ, Scott-Tucker A, Overduin M, Henderson IR | title = Membrane protein architects: the role of the BAM complex in outer membrane protein assembly | journal = Nature Reviews. Microbiology | volume = 7 | issue = 3 | pages = 206–14 | date = March 2009 | pmid = 19182809 | doi = 10.1038/nrmicro2069 | doi-access = free }}</ref><ref name="pmid21370981">{{cite journal | vauthors = Hagan CL, Silhavy TJ, Kahne D | title = β-Barrel membrane protein assembly by the Bam complex | journal = Annual Review of Biochemistry | volume = 80 | pages = 189–210 | date = 2011 | pmid = 21370981 | doi = 10.1146/annurev-biochem-061408-144611 }}</ref><ref name="pmid22221898">{{cite journal | vauthors = Rigel NW, Silhavy TJ | title = Making a beta-barrel: assembly of outer membrane proteins in Gram-negative bacteria | journal = Current Opinion in Microbiology | volume = 15 | issue = 2 | pages = 189–93 | date = April 2012 | pmid = 22221898 | pmc = 3320693 | doi = 10.1016/j.mib.2011.12.007 }}</ref> This complex is responsible in catalyzing folding and insertion of β-barrel proteins into the outer membrane of Gram-negative bacteria.<ref name="pmid22942688">{{cite journal | vauthors = Jiang JH, Tong J, Tan KS, Gabriel K | title = From evolution to pathogenesis: the link between β-barrel assembly machineries in the outer membrane of mitochondria and gram-negative bacteria | journal = International Journal of Molecular Sciences | volume = 13 | issue = 7 | pages = 8038–50 | date = 2012 | pmid = 22942688 | pmc = 3430219 | doi = 10.3390/ijms13078038 | doi-access = free }}</ref><ref name="pmid20616105">{{cite journal | vauthors = Tommassen J | title = Assembly of outer-membrane proteins in bacteria and mitochondria | journal = Microbiology | location = Reading, England | volume = 156 | issue = Pt 9 | pages = 2587–2596 | date = September 2010 | pmid = 20616105 | doi = 10.1099/mic.0.042689-0 | doi-access = free }}</ref>

β-barrel membrane proteins can only be found in the outer membrane of Gram-negative bacteria and in organelles such as mitochondria and chloroplasts which were evolved from bacteria.<ref name="pmid19703392">{{cite journal | vauthors = Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N | title = Importing mitochondrial proteins: machineries and mechanisms | journal = Cell | volume = 138 | issue = 4 | pages = 628–44 | date = August 2009 | pmid = 19703392 | pmc = 4099469 | doi = 10.1016/j.cell.2009.08.005 }}</ref><ref name="pmid22959613">{{cite journal | vauthors = Webb CT, Heinz E, Lithgow T | title = Evolution of the β-barrel assembly machinery | journal = Trends in Microbiology | volume = 20 | issue = 12 | pages = 612–20 | date = December 2012 | pmid = 22959613 | doi = 10.1016/j.tim.2012.08.006 }}</ref> In Gram-negative bacteria, outer membrane proteins are synthesized in the cytoplasm and then exported into the periplasm by Sec translocon machinery.<ref name="pmid20439314">{{cite journal | vauthors = Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J, Lopez R | title = A new bioinformatics analysis tools framework at EMBL-EBI | journal = Nucleic Acids Research | volume = 38 | issue = Web Server issue | pages = W695–9 | date = July 2010 | pmid = 20439314 | pmc = 2896090 | doi = 10.1093/nar/gkq313 }}</ref> Then they are escorted to the inner surface of the outer membrane by molecular chaperons. Finally those nascent proteins interact with BAM Complex and insert into the outer membrane as β-barrel proteins.<ref name="pmid15851030">{{cite journal | vauthors = Wu T, Malinverni J, Ruiz N, Kim S, Silhavy TJ, Kahne D | title = Identification of a multicomponent complex required for outer membrane biogenesis in Escherichia coli | journal = Cell | volume = 121 | issue = 2 | pages = 235–45 | date = April 2005 | pmid = 15851030 | doi = 10.1016/j.cell.2005.02.015 | doi-access = free }}</ref>

== Structure and function == According to the fully resolved BamA structure of ''N. gonorrhoeae'', BamA has a large periplasmic domain connected to a transmembrane β-barrel domain which is made of 16 antiparallel β strands.<ref name="pmid23995689">{{cite journal | vauthors = Noinaj N, Kuszak AJ, Gumbart JC, Lukacik P, Chang H, Easley NC, Lithgow T, Buchanan SK | title = Structural insight into the biogenesis of β-barrel membrane proteins | journal = Nature | volume = 501 | issue = 7467 | pages = 385–90 | date = September 2013 | pmid = 23995689 | pmc = 3779476 | doi = 10.1038/nature12521 }}</ref> There are five polypeptide translocation-associated (POTRA) domains extending from the barrel at the periplasmic domain of BamA. Current studies suggest that the four lipoproteins in the BAM Complex (BamB, BamC, BamD, BamE ) assemble on to the POTRA domains of BamA, making it the vital component of BAM Complex. The first and the last or 16th β-strands associate in closing the barrel. Extracellular loops (eL) eL4, eL6 and eL7 of the barrel forms a dome over the barrel by isolating the interior of the barrel from the extracellular space and interior of the BamA barrel is completely empty.

The external rim of the β-barrel has a narrow, reduced hydrophobic surface and it reduces lipid order and thickness of the membrane around the barrel. Transient separation of 1st and 16th β-strands which are associated in closing the barrel causes lateral opening of the barrel making a route from interior cavity of the BamA into the outer membrane. POTRA 5 domain of BamA sits close to the β–barrel and interacts with periplasmic loops (pL) pL3, pL4, pL5, pL7 and stabilize the closed conformation of the barrel. Swing movements of POTRA 5 domain and having no interactions with pLs make the opening of the barrel. Thus POTRA domains act as a gate to regulate the access into the interior of β–barrel. Hence there are three structural features associate with BamA that regulates the entry of β-barrel proteins into the outer membrane. First, open and closed conformation of BamA β-barrel. Second, the narrow and reduced hydrophobic rim on the surface of the β –barrel causes local destabilization of the outer membrane. Third, ability to undergo lateral opening of the barrel by transient separation of 1st and 16th β–barrel strands.

== References == {{reflist}}

Category:Outer membrane proteins Category:Bacterial proteins