Crystal structure of theMSMEG_4306gene product fromMycobacterium smegmatis

Abstract

The MSMEG_4306 gene from Mycobacterium smegmatis encodes a protein of unknown function with 242 amino-acid residues that contains a conserved zincribbon domain at its C-terminus. Here, the crystal structure of MSMEG_4306 determined by the single-wavelength anomalous dispersion method using just one zinc ion co-purified with the protein is reported. The crystal structure of MSMEG_4306 shows a coiled-coil helix domain in the N-terminal region and a zinc-ribbon domain in the C-terminal region. A structural similarity search against the Protein Data Bank using MSMEG_4306 as a query revealed two similar structures, namely CT398 from Chlamydia trachomatis and HP0958 from Helicobacter pylori, although they share only $15% sequence identity with MSMEG_4306. Based on comparative analysis, it is predicted that MSMEG_4306 may be involved in secretion systems, possibly by interacting with multiple proteins or nucleic acids.

Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase

“…COG1579 is a family of unknown functions (DUF164) that is conserved primarily among bacterial clades, although homologs are found also in archaea. Members of this group have been linked to functional roles in chemotaxis, flagellin synthesis, type III secretion systems (i.e., Helicobacter pylori and Chlamydia trachomatis [ 125 , 170 , 171 , 172 ]), and bacteria-induced host cell maturation (i.e., Mycobacterium avium [ 173 , 174 ]) but the molecular mechanisms involved remain mysterious. The homolog of Mycobacterium tuberculosis has been noted as an essential gene under some circumstances [ 175 ].…”

“…A characteristic feature of the zf-RING_7 family is the presence of a C4-type zinc-ribbon domain with two pairs of cysteines in a CxxC-x (18–26)-CxxC (zinc-finger) motif capable of binding zinc ions. Published structures (5Y06/5Y05 of M. smegmatis [ 171 ]; 4ILO of Chlamydia trachomatis [ 172 ]) demonstrate an unusual coiled-coil structure that is book-ended by the aforementioned distinctive zinc-finger domain.…”

Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase

“…COG1579, is a family of unknown function (DUF164) that is conserved primarily among bacterial clades, although homologs are found also in archaea. Members of this group have been linked to functional roles in chemotaxis, flagellin synthesis, type III secretion systems (i.e., Helicobacter pylori and Chlamydia trachomatis [120,[163][164][165]), and bacteria-induced host cell maturation (i.e., Mycobacterium avium [166,167]) but the molecular mechanisms involved remain mysterious. The homolog of Mycobacterium tuberculosis has been noted as an essential gene under some circumstances [168].…”

“…A characteristic feature of the zf-RING_7 family is the presence of a C4-type zinc-ribbon domain with two pairs of cysteines in a CxxC-x (18-26)-CxxC (zinc-finger) motif capable of binding zinc ions. Published structures (5Y06/5Y05 of M. smegmatis [164]; 4ILO of Chlamydia trachomatis [165]) demonstrate an unusual coiled-coil structure that is book-ended by the aforementioned distinctive zinc-finger domain. Despite the high clustering frequencies discernible for several co-occurring COGs, a single link between DUF34 homologs and a distinct metabolic area remained unclear.…”