Molecular structure and peptidoglycan recognition of Mycobacterium tuberculosis ArfA (Rv0899). J Mol Biol 2012 Feb 17;416(2):208-20
Date
12/31/2011Pubmed ID
22206986Pubmed Central ID
PMC3269530DOI
10.1016/j.jmb.2011.12.030Scopus ID
2-s2.0-84856438110 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Mycobacterium tuberculosis ArfA (Rv0899) is a membrane protein encoded by an operon that is required for supporting bacterial growth in acidic environments. 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. Previously, we showed that ArfA forms three independently structured modules, and we reported the structure of its central domain (B domain). Here, we describe the high-resolution structure and dynamics of the C domain, we identify ArfA as a peptidoglycan-binding protein and we elucidate the molecular basis for its specific recognition of diaminopimelate-type peptidoglycan. The C domain of ArfA adopts the characteristic fold of the OmpA-like family. 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 M. tuberculosis and also associates with a soluble peptide intermediate of peptidoglycan biosynthesis. This enabled us to characterize the peptidoglycan binding site where five highly conserved ArfA residues, including two key arginines, establish the specificity for diaminopimelate- but not Lys-type peptidoglycan. ArfA is the first peptidoglycan-binding protein to be identified in M. 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.
Author List
Yao Y, Barghava N, Kim J, Niederweis M, Marassi FMAuthor
Francesca M. Marassi PhD Chair, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Bacterial Outer Membrane ProteinsBinding Sites
Crystallography, X-Ray
Diaminopimelic Acid
Hydrogen-Ion Concentration
Models, Molecular
Mycobacterium tuberculosis
Peptidoglycan
Protein Conformation
