4zvg
Crystal structure of GGDEF domain of the E. coli DosC - form III
Structural highlights
FunctionDOSC_ECOLI Globin-coupled heme-based oxygen sensor protein displaying diguanylate cyclase (DGC) activity in response to oxygen availability. Thus, catalyzes the synthesis of cyclic diguanylate (c-di-GMP) via the condensation of 2 GTP molecules. Is involved in the modulation of intracellular c-di-GMP levels, in association with DosP which catalyzes the degradation of c-di-GMP (PDE activity). Cyclic-di-GMP is a second messenger which controls cell surface-associated traits in bacteria. DosC regulates biofilm formation through the oxygen-dependent activation of the csgBAC operon, which encodes curli structural subunits, while not affecting the expression of the regulatory operon csgDEFG. DosC, but not the other DGCs in E.coli, also promotes the production of the exopolysaccharide poly-N-acetylglucosamine (PNAG) through up-regulation of the expression of the PNAG biosynthetic pgaABCD operon, independently of CsrA. Overexpression leads to an increased level of c-di-GMP, which leads to changes in the cell surface, to abnormal cell division, increased biofilm formation and decreased swimming (the latter 2 in strain W3110). In a strain able to produce cellulose (strain TOB1, a fecal isolate) overexpression leads to an increase in cellulose production. Publication Abstract from PubMedCyclic di-GMP is a bacterial second messenger that is involved in switching between motile and sessile lifestyles. Given the medical importance of biofilm formation, there has been increasing interest in understanding the synthesis and degradation of cyclic di-GMPs and their regulation in various bacterial pathogens. Environmental cues are detected by sensing domains coupled to GGDEF and EAL or HD-GYP domains that have diguanylate cyclase and phosphodiesterase activities, respectively, producing and degrading cyclic di-GMP. The Escherichia coli protein DosC (also known as YddV) consists of an oxygen-sensing domain belonging to the class of globin sensors that is coupled to a C-terminal GGDEF domain via a previously uncharacterized middle domain. DosC is one of the most strongly expressed GGDEF proteins in E. coli, but to date structural information on this and related proteins is scarce. Here, the high-resolution structural characterization of the oxygen-sensing globin domain, the middle domain and the catalytic GGDEF domain in apo and substrate-bound forms is described. The structural changes between the iron(III) and iron(II) forms of the sensor globin domain suggest a mechanism for oxygen-dependent regulation. The structural information on the individual domains is combined into a model of the dimeric DosC holoprotein. These findings have direct implications for the oxygen-dependent regulation of the activity of the cyclase domain. Structural analysis of an oxygen-regulated diguanylate cyclase.,Tarnawski M, Barends TR, Schlichting I Acta Crystallogr D Biol Crystallogr. 2015 Nov;71(Pt 11):2158-77. doi:, 10.1107/S139900471501545X. Epub 2015 Oct 27. PMID:26527135[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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