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A repurposed, non-canonical cytochrome c, chaperones calcium binding by PilY1 for type IVa pili formation - Dataset 2/2

ABSTRACT: Type IVa pili (T4aP) are versatile bacterial cell surface structures that undergo extension/adhesion/retraction cycles powered by the cell envelope-spanning T4aP machine. In this machine, a complex composed of four minor pilins and PilY1 primes T4aP extension and is also present at the pilus tip mediating adhesion. Similar to many other bacteria, Myxococcus xanthus contains multiple minor pilins/PilY1 sets, the function of which remains unknown.Here, we report that minor pilins and PilY1 of cluster_1 (PilY1.1) form calcium-responsive priming and tip complexes contingent on a non-canonical cytochrome c (TfcP) with an unusual His/Cys heme ligation. We provide evidence that TfcP is unlikely to participate in electron transport and has been repurposed to promote calcium binding by PilY1.1 at low calcium concentrations, thereby stabilising PilY1.1 and enabling its function in a broader range of calcium concentrations. These results identify a novel function of cytochromes c and illustrate how incorporating an accessory factor expands the environmental range under which the T4aP system functions.

INSTRUMENT(S): Exactive Plus

ORGANISM(S): Myxococcus Xanthus Dk 1622

SUBMITTER: Timo Glatter

LAB HEAD: Timo Glatter

PROVIDER: PXD031267 | Pride | 2022-01-30

REPOSITORIES: Pride

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Project description:Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity. ## File Key ### MS-ABPP The following raw files were acquired on an Eclipse instrument in triplicate with two concentrations of inhibitor in both brain and kidney. These variables are encoded in the file names. Associated analysis pipeline files from CIMAGE are provided for each raw file (same file name, with a .raw_output_rt_10_sn_2.5.to_excel extension). - brain_conc1.0_rep1.raw - brain_conc1.0_rep2.raw - brain_conc1.0_rep3.raw - brain_conc10.0_rep1.raw - brain_conc10.0_rep2.raw - brain_conc10.0_rep3.raw - kidney_conc1.0_rep1.raw - kidney_conc1.0_rep2.raw - kidney_conc1.0_rep3.raw - kidney_conc10.0_rep1.raw - kidney_conc10.0_rep2.raw - kidney_conc10.0_rep3.raw ### TMT Dose Response The following raw files were acquired on an Eclipse instrument instrument in both brain and white adipose tissues: - brain_dose_response.raw - wat_dose_response.raw The TMT channels were organized as follows: - DMSO channels: 1, 3, 5 - ABD-110 @ 0.001 μM: 7, 9, 11 - ABD-110 @ 0.01 μM: 2, 4, 6 - ABD-110 @ 0.1 μM: 13, 15, 17 - ABD-110 @ 1 μM: 8, 10, 12 - ABD-110 @ 10 μM: 14, 16, 18 Associated analysis pipeline files after IDFilter run are provided for each file (same file name, with a _filtered_matches suffix and an .idXML extension). ### PRM AIG1 In Vivo Target Engagement The A prefix before the replicate number refers to treatment with ABD-110, whereas the V prefix refers to vehicle treatment. Diet and tissue type are also encoded in the filename. The following files were acquired on a Lumos instrument, with 5 replicates for each condition (as noted in square brackets). Associated pipeline analysis files are Skyline exports and are provided as two .csv files having names beginning with Skyline_PRM_export and ending with the tissue types contained. - Brain_Chow_A[1-5].raw - Brain_Chow_V[1-5].raw - Brain_HVD_A[1-5].raw - Brain_HVD_V[1-5].raw - eWAT_Chow_A[1-5].raw - eWAT_Chow_V[1-5].raw - eWAT_HVD_A[1-5].raw - eWAT_HVD_V[1-5].raw - iWAT_Chow_A[1-5].raw - iWAT_Chow_V[1-5].raw - iWAT_HVD_A[1-5].raw - iWAT_HVD_V[1-5].raw - Kindey_Chow_A[1-5].raw - Kindey_Chow_V[1-5].raw - Kindey_HVD_A[1-5].raw - Kindey_HVD_V[1-5].raw

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			Action	DRS
	MH-0363-11-txt.zip	Other
	MH_0363-11-10PRM2.raw	Raw
	MH_0363-11-11PRM2.raw	Raw
	MH_0363-11-12PRM2.raw	Raw
	MH_0363-11-13PRM2.raw	Raw

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A repurposed, non-canonical cytochrome c, chaperones calcium binding by PilY1 for type IVa pili formation - Dataset 2/2

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