Structural Insights into Oxygen-Dependent Signal Transduction within Globin Coupled Sensors

Shannon Rivera, Paul G. Young, Eric D. Hoffer, Gregory E. Vansuch, Carmen L. Metzler, Christine M. Dunham, Emily E. Weinert

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


In order to respond to external stimuli, bacteria have evolved sensor proteins linking external signals to intracellular outputs that can then regulate downstream pathways and phenotypes. Globin coupled sensor proteins (GCSs) serve to link environmental O2 levels to cellular processes by coupling a heme-containing sensor globin domain to a catalytic output domain. However, the mechanism by which O2 binding activates these proteins is currently unknown. To provide insights into the signaling mechanism, two distinct dimeric complexes of the isolated globin domain of the GCS from Bordetella pertussis (BpeGlobin) were solved via X-ray crystallography in which differences in ligand-bound states were observed. Both monomers of one dimer contain Fe(II)-O2 states, while the other dimer consists of the Fe(III)-H2O and Fe(II)-O2 states. These data provide the first molecular insights into the heme pocket conformation of the active Fe(II)-O2 form of these enzymes. In addition, heme distortion modes and heme-protein interactions were found to correlate with the ligation state of the globin, suggesting that these conformational changes play a role in O2-dependent signaling. Fourier transform infrared spectroscopy (FTIR) of the full-length GCS from B. pertussis (BpeGReg) and the closely related GCS from Pectobacterium carotovorum ssp. carotovorum (PccGCS) confirmed the importance of an ordered water within the heme pocket and two distal residues (Tyr43 and Ser68) as hydrogen-bond donors. Taken together, this work provides mechanistic insights into BpeGReg O2 sensing and the signaling mechanisms of diguanylate cyclase-containing GCS proteins.

Original languageEnglish (US)
Pages (from-to)14386-14395
Number of pages10
JournalInorganic chemistry
Issue number22
StatePublished - Nov 19 2018

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry


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