Bam A

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.^[1] BAM Complex consists of five components; BamB, BamC, BamD, BamE (all are lipoproteins) and BamA (Outer membrane protein).^[2][3][4][5] This complex is responsible in catalyzing folding and insertion of β-barrel proteins into the outer membrane of Gram-negative bacteria.^[6][7]

OMP insertion (BamComplex) porin
Identifiers
Symbol	BamA
Pfam	PF01103
InterPro	IPR023707
TCDB	1.B.33
OPM superfamily	179
OPM protein	5ayw
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.^[8][9] In Gram-negative bacteria, outer membrane proteins are synthesized in the cytoplasm and then exported into the periplasm by Sec translocon machinery.^[10] 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.^[11]

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.^[12] 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.