Mycobacterium tuberculosis ArfA Rv0899

Function

Protein Rv0899 from Mycobacterium tuberculosis [1] belongs to the OmpA (outer membrane protein A) family of outer membrane proteins.The deletion of this gene impairs the uptake of some water-soluble substances, such as serine, glucose, and glycerol.Using NMR chemical shift perturbation and isothermal calorimetric titration assays, Rv0899 was able to interact with Zn(2+) ions, which may indicate a role for Rv0899 in the process of Zn(2+) acquisition. ^[1] Mycobacterium tuberculosis ArfA (Rv0899) is a membrane protein encoded by an ammonia release facilator operon that is necessary for rapid ammonia secretion, pH neutralization and adaptation to acidic environments in vitro. Its C-terminal domain (C domain) shares significant sequence homology with the OmpA-like family of peptidoglycan-binding domains, suggesting that its physiological function in acid stress protection may be related to its interaction with the mycobacterial cell wall. It exhibits pH-dependent conformational dynamics (with significant heterogeneity at neutral pH and a more ordered structure at acidic pH), which could be related to its acid stress response. The C domain associates tightly with polymeric peptidoglycan isolated from Mycobacterium tuberculosis. Its functions in acid stress protection and peptidoglycan binding suggest a link between the acid stress response and the physicochemical properties of the mycobacterial cell wall.^[2].

Structure Section

The 326-residue protein contains three domains: an N-terminal domain (residues 1-72) that includes a sequence of 20 hydrophobic amino acids required for membrane translocation, a central B domain (residues 73-200) with homology to the conserved putative lipid-binding BON (bacterial OsmY and nodulation) superfamily[2] ,, and a C domain (residues 201-326) with homology to the OmpA-C-like superfamily of periplasmic peptidoglycan-binding sequences, found in several types of bacterial membrane proteins. Residues 73-326 form a mixed alpha/beta-globular structure, encompassing two independently folded modules corresponding to the B and C domains connected by a flexible linker. The B domain folds with . .

Disease

Rv0899 has been proposed to act as an outer membrane porin and to contribute to the bacterium's adaptation to the acidic environment of the phagosome[3] during infection. The gene is restricted to pathogenic mycobacteria and, thus, is an attractive candidate for the development of anti-tuberculosis chemotherapy. ^[3] Probably plays a role in ammonia secretion that neutralizes the medium at pH 5.5,and preceded exponential growth of Mycobacterium tuberculosis, although it does not play a direct role in ammonia transport.[ARFA_MYCTU]. The ompATb operon is necessary for rapid ammonia secretion and adaptation of M. tuberculosis to acidic environments in vitro but not in mice. ^[4]

Relevance

Structural highlights