9.B.121 The AsmA (AsmA) Family
AsmA mutations were isolated as extragenic suppressors of an OmpF assembly mutant, OmpF315 in E. coli (Deng and Misra, 1996). This suppressor locus encoded a protein that was present in low levels and could only be visualized by Western blotting in cells where AsmA was overproduced. AsmA localized with the inner membrane, but the mutant OmpF assembly step influenced by AsmA occurred in the outer membrane. AsmA null mutations reduced lipopolysaccharide (LPS) levels, thereby lowering the ratios of glycerolphospholipids to LPS and envelope proteins to LPS in the outer membrane. Despite these quantitative alterations, no apparent structural changes in LPS or major phospholipids were noted. Reduced LPS levels in asmA mutants indicated a possible role of AsmA in LPS biogenesis (Deng and Misra, 1996).
Bacterial AsmA-like proteins appear to bridge the gap in intermembrane phospholipid transport (Kumar and Ruiz 2023). In eukaryotic cells, nonvesicular lipid transport between organelles is mediated by lipid-transfer proteins. A class of these lipid transporters has been described to facilitate the bulk of inter-organelle lipid transport at contact sites by forming bridge-like structures with a hydrophobic groove through which lipids travel. Because their predicted structures are composed of repeating β-groove (RBG) domains, they have been named the RBG protein superfamily. Early studies on RBG proteins VPS13 and ATG2 recognized the resemblance of their predicted structures to that of the bacterial Lpt system, which transports newly synthesized lipopolysaccharides (LPS) between the inner and the outer membranes (IMs and OMs) of Gram-negative bacteria. In these didermic bacteria, the IMs and OMs are separated by an aqueous periplasmic compartment that is traversed by a bridge-like structure built with β-jelly roll domains from several Lpt proteins that provides a hydrophobic groove for LPS molecules to travel across the periplasm. Despite structural and functional similarities between RBG proteins and the Lpt system, the bacterial AsmA-like protein family has recently emerged as the likely ancestor of RBG proteins and long sought-after transporters that facilitate the transfer of phospholipids from the IM to the OM. Kumar and Ruiz 2023 reviewed the structures and functions of bacterial AsmA-like proteins, mainly focusing on studies that have led to the proposal that AsmA-like proteins mediate the bulk of phospholipid transfer between the IMs and OMs.
Gram-negative bacteria display either a flat or an irregular outer
membrane. The periodontal pathogen Aggregatibacter (Actinobacillus)
actinomycetemcomitans has an irregular outer membrane. Gallant et al. 2008 have
identified a gene that is associated with the biogenesis of this
morphology. The gene is part of a three-gene operon and codes for a
141-kDa protein designated morphogenesis protein C (MorC), which is
conserved in several gram-negative bacteria including Haemophilus
influenzae and Pasteurella multocida. Insertional inactivation of this
gene resulted in the conversion of an irregularly shaped membrane to a
flat membrane. Associated with this morphological change were the
autoaggregation of the bacteria during planktonic growth and a
concomitant increase in the surface hydrophobicity of the bacterium.
The absence of MorC also resulted in the loss of the secretion of
leukotoxin but not of ltxA transcription. MorC apparently is critical for membrane morphology and leukotoxin secretion in A.
actinomycetemcomitans (Gallant et al. 2008).