6rfm | pdb_00006rfm

Bordetella pertussis adenylate cyclase toxin transmembrane segment 411-490 in DPC micelles

spinqualitylabelsall models 6rfm, 50 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6rfm is a 1 chain structure with sequence from "bacterium_tussis-convulsivae"_lehmann_and_neumann_1927 "bacterium tussis-convulsivae" lehmann and neumann 1927. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: cya, cyaA, BN118_0468 ("Bacterium tussis-convulsivae" Lehmann and Neumann 1927) Activity: Adenylate cyclase, with EC number 4.6.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CYAA_BORP1] This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function. Publication Abstract from PubMed Two distinct conformers of the adenylate cyclase toxin (CyaA) appear to accomplish its two parallel activities within target cell membrane. The translocating conformer would deliver the N-terminal adenylyl cyclase (AC) enzyme domain across plasma membrane into cytosol of cells, while the pore precursor conformer would assemble into oligomeric cation-selective pores and permeabilize cellular membrane. Both toxin activities then involve a membrane-interacting 'AC-to-Hly-linking segment' (residues 400 to 500). Here, we report the NMR structure of the corresponding CyaA411-490 polypeptide in dodecylphosphocholine micelles and show that it consists of two alpha-helices linked by an unrestrained loop. The N-terminal alpha-helix (Gly418 to His439) remained solvent accessible, while the C-terminal alpha-helix (His457 to Phe485) was fully enclosed within detergent micelles. CyaA411-490 weakly bound Ca(2+) ions (apparent KD 2.6 mM) and permeabilized negatively charged lipid vesicles. At high concentrations (10 muM) the CyaA411-490 polypeptide formed stable conductance units in artificial lipid bilayers with applied voltage, suggesting its possible transmembrane orientation in the membrane-inserted toxin. Mutagenesis revealed that two clusters of negatively charged residues within the 'AC-to-Hly-linking segment' (Glu419 to Glu432 and Asp445 to Glu448) regulate the balance between the AC domain translocating and pore-forming capacities of CyaA in function of calcium concentration. Negative charge of the AC-to-Hly linking segment modulates calcium-dependent membrane activities of Bordetella adenylate cyclase toxin.,Sukova A, Bumba L, Srb P, Veverka V, Stanek O, Holubova J, Chmelik J, Fiser R, Sebo P, Masin J Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183310. doi:, 10.1016/j.bbamem.2020.183310. Epub 2020 Apr 22. PMID:32333856 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA