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LUD, a new protein domain associated with lactate utilization.

Hwang WC, Bakolitsa C, Punta M, Coggill PC, Bateman A, Axelrod HL, Rawlings ND, Sedova M, Peterson SN, Eberhardt RY, Aravind L, Pascual J, Godzik A - BMC Bioinformatics (2013)

Bottom Line: We have observed that the LUD domain has an increased abundance in the human gut microbiome.We propose a model for the substrate and cofactor binding and regulation in LUD domain.The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joint Center for Structural Genomics, La Jolla, CA 92037, USA. wchwang@sanfordburnham.org.

ABSTRACT

Background: A novel highly conserved protein domain, DUF162 [Pfam: PF02589], can be mapped to two proteins: LutB and LutC. Both proteins are encoded by a highly conserved LutABC operon, which has been implicated in lactate utilization in bacteria. Based on our analysis of its sequence, structure, and recent experimental evidence reported by other groups, we hereby redefine DUF162 as the LUD domain family.

Results: JCSG solved the first crystal structure [PDB:2G40] from the LUD domain family: LutC protein, encoded by ORF DR_1909, of Deinococcus radiodurans. LutC shares features with domains in the functionally diverse ISOCOT superfamily. We have observed that the LUD domain has an increased abundance in the human gut microbiome.

Conclusions: We propose a model for the substrate and cofactor binding and regulation in LUD domain. The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed.

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Gene and protein make-up of the three elements of the LutABC operon. The three genes making up the LutABC operon and the corresponding various proteins with their Pfam domains marked are shown.
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Figure 5: Gene and protein make-up of the three elements of the LutABC operon. The three genes making up the LutABC operon and the corresponding various proteins with their Pfam domains marked are shown.

Mentions: LUD domain is a protein domain of approximately 160 residues in length (Figure 4, and Additional file 1). It is found in two proteins encoded by the highly conserved LutABC operon (Figures 5 and 6), which appears in a wide variety of Gram-positive and Gram-negative bacteria [9]. The LutABC operon was found to be important for growth and biofilm formation in Bacillus subtilis[9]. The LUD domain is found in both LutB and LutC proteins encoded by the LutABC operon. In the vast majority of cases, the LUD domain is the only constituent domain of LutC proteins, whereas in LutB proteins it is often associated with protein families Fer4_8, CCG, or DUF3390 (Figure 5). Indeed, in Pfam release 27.0 there is just one instance of LutB protein being made of DUF162 alone, which occurs in Deinococcus radiodurans (Figure 6). However, searching the section of DNA in Deinococcus radiodurans from the start of lutB to the start of lutC finds a frame-shift and a copy of DUF3390 on the opposite strand, though no apparent Fer4_8, implying possible poor quality sequencing in this region. Finally, LutA protein is most often made of two copies of CCG domains. Both Fer4_8 and CCG domains are likely iron-sulfur cluster binding domains [17]. LutA protein is a putative iron-sulfur heterodisulfide reductase; LutB protein a putative iron-sulfur oxidoreductase; LutC protein a putative subunit of an iron-sulfur protein. Together, they are thought to mediate the oxidation of lactate via a cytochrome-like electron transfer chain, though the precise roles played by LutABC remain unclear [9].


LUD, a new protein domain associated with lactate utilization.

Hwang WC, Bakolitsa C, Punta M, Coggill PC, Bateman A, Axelrod HL, Rawlings ND, Sedova M, Peterson SN, Eberhardt RY, Aravind L, Pascual J, Godzik A - BMC Bioinformatics (2013)

Gene and protein make-up of the three elements of the LutABC operon. The three genes making up the LutABC operon and the corresponding various proteins with their Pfam domains marked are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924224&req=5

Figure 5: Gene and protein make-up of the three elements of the LutABC operon. The three genes making up the LutABC operon and the corresponding various proteins with their Pfam domains marked are shown.
Mentions: LUD domain is a protein domain of approximately 160 residues in length (Figure 4, and Additional file 1). It is found in two proteins encoded by the highly conserved LutABC operon (Figures 5 and 6), which appears in a wide variety of Gram-positive and Gram-negative bacteria [9]. The LutABC operon was found to be important for growth and biofilm formation in Bacillus subtilis[9]. The LUD domain is found in both LutB and LutC proteins encoded by the LutABC operon. In the vast majority of cases, the LUD domain is the only constituent domain of LutC proteins, whereas in LutB proteins it is often associated with protein families Fer4_8, CCG, or DUF3390 (Figure 5). Indeed, in Pfam release 27.0 there is just one instance of LutB protein being made of DUF162 alone, which occurs in Deinococcus radiodurans (Figure 6). However, searching the section of DNA in Deinococcus radiodurans from the start of lutB to the start of lutC finds a frame-shift and a copy of DUF3390 on the opposite strand, though no apparent Fer4_8, implying possible poor quality sequencing in this region. Finally, LutA protein is most often made of two copies of CCG domains. Both Fer4_8 and CCG domains are likely iron-sulfur cluster binding domains [17]. LutA protein is a putative iron-sulfur heterodisulfide reductase; LutB protein a putative iron-sulfur oxidoreductase; LutC protein a putative subunit of an iron-sulfur protein. Together, they are thought to mediate the oxidation of lactate via a cytochrome-like electron transfer chain, though the precise roles played by LutABC remain unclear [9].

Bottom Line: We have observed that the LUD domain has an increased abundance in the human gut microbiome.We propose a model for the substrate and cofactor binding and regulation in LUD domain.The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joint Center for Structural Genomics, La Jolla, CA 92037, USA. wchwang@sanfordburnham.org.

ABSTRACT

Background: A novel highly conserved protein domain, DUF162 [Pfam: PF02589], can be mapped to two proteins: LutB and LutC. Both proteins are encoded by a highly conserved LutABC operon, which has been implicated in lactate utilization in bacteria. Based on our analysis of its sequence, structure, and recent experimental evidence reported by other groups, we hereby redefine DUF162 as the LUD domain family.

Results: JCSG solved the first crystal structure [PDB:2G40] from the LUD domain family: LutC protein, encoded by ORF DR_1909, of Deinococcus radiodurans. LutC shares features with domains in the functionally diverse ISOCOT superfamily. We have observed that the LUD domain has an increased abundance in the human gut microbiome.

Conclusions: We propose a model for the substrate and cofactor binding and regulation in LUD domain. The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed.

Show MeSH