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Structural highlights

Function

CYDC_ECOLI Part of the ABC transporter complex CydDC that exports the reduced low-molecular-weight thiols cysteine and glutathione to the periplasm (PubMed:12393891, PubMed:16040611). Export of these thiol-containing redox-active molecules may be crucial for redox homeostasis in the periplasm, permitting correct assembly of various respiratory complexes and formation of correct disulfide bonds in periplasmic and secreted proteins (Probable). CydC contains transmembrane domains (TMD), which form a pore in the inner membrane, and an ATP-binding domain (NBD), which is responsible for energy generation (PubMed:24958725). Required for the assembly of functional cytochrome bd-type quinol oxidases and periplasmic c-type cytochromes (PubMed:3032907, PubMed:7934832, PubMed:8181727, PubMed:15470119). Overexpression of CydDC under anaerobic conditions also results in the formation of a heme biosynthesis-derived pigment, P-574 (PubMed:12375104). CydDC binds heme b, but heme is probably not transported by the complex and instead has a role in regulating ATPase activity (PubMed:24958725).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]} Conversely, a more recent study suggests an alternative function of CydDC: authors suggest that CydDC does not mediate the export of L-cysteine but rather reduces cytoplasmic L-cystine to L-cysteine (PubMed:32900959). The principle function of CydDC would be to maintain the reduced state of cytoplasmic L-cysteine, thereby providing an important connection between sulfur metabolism, oxidative stress and resistance to antibiotics (PubMed:32900959).^[12]

References

1. ↑ Cook GM, Cruz-Ramos H, Moir AJ, Poole RK. A novel haem compound accumulated in Escherichia coli overexpressing the cydDC operon, encoding an ABC-type transporter required for cytochrome assembly. Arch Microbiol. 2002 Nov;178(5):358-69. PMID:12375104 doi:10.1007/s00203-002-0467-6
2. ↑ Pittman MS, Corker H, Wu G, Binet MB, Moir AJ, Poole RK. Cysteine is exported from the Escherichia coli cytoplasm by CydDC, an ATP-binding cassette-type transporter required for cytochrome assembly. J Biol Chem. 2002 Dec 20;277(51):49841-9. PMID:12393891 doi:10.1074/jbc.M205615200
3. ↑ Cruz-Ramos H, Cook GM, Wu G, Cleeter MW, Poole RK. Membrane topology and mutational analysis of Escherichia coli CydDC, an ABC-type cysteine exporter required for cytochrome assembly. Microbiology (Reading). 2004 Oct;150(Pt 10):3415-27. PMID:15470119 doi:10.1099/mic.0.27191-0
4. ↑ Pittman MS, Robinson HC, Poole RK. A bacterial glutathione transporter (Escherichia coli CydDC) exports reductant to the periplasm. J Biol Chem. 2005 Sep 16;280(37):32254-61. PMID:16040611 doi:10.1074/jbc.M503075200
5. ↑ Yamashita M, Shepherd M, Booth WI, Xie H, Postis V, Nyathi Y, Tzokov SB, Poole RK, Baldwin SA, Bullough PA. Structure and function of the bacterial heterodimeric ABC transporter CydDC: stimulation of ATPase activity by thiol and heme compounds. J Biol Chem. 2014 Aug 15;289(33):23177-23188. PMID:24958725 doi:10.1074/jbc.M114.590414
6. ↑ Georgiou CD, Fang H, Gennis RB. Identification of the cydC locus required for expression of the functional form of the cytochrome d terminal oxidase complex in Escherichia coli. J Bacteriol. 1987 May;169(5):2107-12. PMID:3032907 doi:10.1128/jb.169.5.2107-2112.1987
7. ↑ Poole RK, Hatch L, Cleeter MW, Gibson F, Cox GB, Wu G. Cytochrome bd biosynthesis in Escherichia coli: the sequences of the cydC and cydD genes suggest that they encode the components of an ABC membrane transporter. Mol Microbiol. 1993 Oct;10(2):421-30 PMID:7934832
8. ↑ Poole RK, Gibson F, Wu G. The cydD gene product, component of a heterodimeric ABC transporter, is required for assembly of periplasmic cytochrome c and of cytochrome bd in Escherichia coli. FEMS Microbiol Lett. 1994 Apr 1;117(2):217-23. PMID:8181727 doi:10.1111/j.1574-6968.1994.tb06768.x
9. ↑ Pittman MS, Corker H, Wu G, Binet MB, Moir AJ, Poole RK. Cysteine is exported from the Escherichia coli cytoplasm by CydDC, an ATP-binding cassette-type transporter required for cytochrome assembly. J Biol Chem. 2002 Dec 20;277(51):49841-9. PMID:12393891 doi:10.1074/jbc.M205615200
10. ↑ Pittman MS, Robinson HC, Poole RK. A bacterial glutathione transporter (Escherichia coli CydDC) exports reductant to the periplasm. J Biol Chem. 2005 Sep 16;280(37):32254-61. PMID:16040611 doi:10.1074/jbc.M503075200
11. ↑ Poole RK, Cozens AG, Shepherd M. The CydDC family of transporters. Res Microbiol. 2019 Nov-Dec;170(8):407-416. PMID:31279084 doi:10.1016/j.resmic.2019.06.003
12. ↑ Mironov A, Seregina T, Shatalin K, Nagornykh M, Shakulov R, Nudler E. CydDC functions as a cytoplasmic cystine reductase to sensitize Escherichia coli to oxidative stress and aminoglycosides. Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23565-23570. PMID:32900959 doi:10.1073/pnas.2007817117