Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen

Pinelo, Jose E.E.; Manandhar, Pragya; Popovic, Grega; Ray, Katherine; Tasdelen, Mehmet F.; Nguyen, Quoc; Iavarone, Anthony T.; Offenbacher, Adam R.; Hudson, Nathan E.; Şen, Mehmet

doi:10.1016/j.jtha.2023.01.034

Cited by 5 publications

(2 citation statements)

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“…Previous studies have indicated an association between elevated SII and tuberculosis, with a correlation observed with anxiety ( Liu et al, 2022 ). Fibrinogen, a coagulation system activator, shows heightened levels in tuberculosis infections ( Kager et al, 2015 ; Pinelo et al, 2023 ). Their roles in the differential diagnosis of suspected tuberculosis remain underexplored.…”

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confidence: 99%

Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research

Yu,

Shang,

Huang

et al. 2024

Front. Microbiol.

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BackgroundThe clinical challenge of differentiating suspected tuberculosis with positive T-SPOT.TB results persist. This study aims to investigate the utility of the Systemic Immune-Inflammation Index (SII), Fibrinogen, and T-SPOT.TB in distinguishing between active pulmonary tuberculosis (PTB) and non-tuberculous lung diseases.MethodsA retrospective analysis included 1,327 cases of active PTB with positive T-SPOT.TB results and 703 cases of non-tuberculous lung diseases from May 2016 to December 2020 at Meizhou People’s Hospital. These were designated as the case group and the control group, respectively. The detection indicators of T-SPOT.TB: Early Secreted Antigenic Target 6 (ESAT-6), Culture Filtrate Protein 10 (CFP-10), as well as SII and Fibrinogen levels—were compared and analyzed for association and joint diagnostic value between the two groups.ResultsThe case group showed higher values of ESAT-6, CFP-10, SII, and Fibrinogen compared to the control group (all p < 0.001). In the case group, SII and Fibrinogen did not correlate with ESAT-6 and CFP-10 (∣rs∣ all < 0.3) but were positively correlated with C-reactive protein (CRP; rs all > 0.3). SII and Fibrinogen values in smear-positive pulmonary tuberculosis were higher than in smear-negative cases (all p < 0.05). The optimal diagnostic thresholds for ESAT-6, CFP-10, SII, and Fibrinogen in differentiating between active PTB and non-tuberculous lung diseases were 21.50 SFCs/106 PBMC, 22.50 SFCs/106 PBMC, 2128.32, and 5.02 g/L, respectively. Regression logistic analysis showed that ESAT-6 < 21.5 (OR: 1.637, 95% CI: 1.311–2.043, p < 0.001), CFP-10 < 22.5 (OR: 3.918, 95% CI: 3.138–4.892, p = 0.025), SII < 2128.32 (OR: 0.763, 95% CI: 0.603–0.967, p < 0.001), and FIB < 5.02 (OR: 2.287, 95% CI: 1.865–2.806, p < 0.001) were independent risk factors for active PTB. The specificity for ESAT-6 + CFP-10, ESAT-6 + CFP-10 + SII, ESAT-6 + CFP-10 + FIB, and ESAT-6 + CFP-10 + SII + FIB was 82.5%, 83.2%, 95.8%, and 80.1%, respectively, while sensitivity was 52.6%, 53.0%, 55.8%, and 44.7%, and positive predictive values were 85.0%, 85.6%, 84.1%, and 89.6%, respectively.ConclusionSII and Fibrinogen are positively correlated with the degree of tuberculosis inflammation and the bacterial load of Mycobacterium tuberculosis. The combined detection of SII, Fibrinogen, and T-SPOT.TB is significant in distinguishing between active PTB with positive T-SPOT.TB results and non-tuberculous lung diseases.

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Section: Introductionmentioning

confidence: 99%

Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research

Yu,

Shang,

Huang

et al. 2024

Front. Microbiol.

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“…They facilitate protein folding, protein trafficking for secretion, and/or membrane presentation. , Glycans also have been shown to help stabilize protein structure and to protect against proteolysis . Mis- or altered glycosylation has been associated with over 125 disease states in humans, including the congenital disorders rheumatoid arthritis and diabetes, presumably functioning through altered cellular recognition and/or changes to the protein structure and stability. − One of the inherent challenges in studying glycoproteins is the difficulty in characterizing their structure by conventional X-ray diffraction methods, as the branched and dynamic nature of the (sometimes heterogeneous) carbohydrate assemblies can inhibit crystallization …”

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confidence: 99%

Impact of N-Glycosylation on Protein Structure and Dynamics Linked to Enzymatic C–H Activation in the M. oryzae Lipoxygenase

Whittington,

Sharma,

Hill

et al. 2024

Biochemistry

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Lipoxygenases (LOXs) from pathogenic fungi are potential therapeutic targets for defense against plant and select human diseases. In contrast to the canonical LOXs in plants and animals, fungal LOXs are unique in having appended N-linked glycans. Such important post-translational modifications (PTMs) endow proteins with altered structure, stability, and/or function. In this study, we present the structural and functional outcomes of removing or altering these surface carbohydrates on the LOX from the devastating rice blast fungus, M. oryzae, MoLOX. Alteration of the PTMs did notinfluence the active site enzyme−substrate ground state structures as visualized by electron−nuclear double resonance (ENDOR) spectroscopy. However, removal of the eight N-linked glycans by asparagine-toglutamine mutagenesis nonetheless led to a change in substrate selectivity and an elevated activation energy for the reaction with substrate linoleic acid, as determined by kinetic measurements. Comparative hydrogen−deuterium exchange mass spectrometry (HDX-MS) analysis of wild-type and Asn-to-Gln MoLOX variants revealed a regionally defined impact on the dynamics of the arched helix that covers the active site. Guided by these HDX results, a single glycan sequon knockout was generated at position 72, and its comparative substrate selectivity from kinetics nearly matched that of the Asn-to-Gln variant. The cumulative data from model glyco-enzyme MoLOX showcase how the presence, alteration, or removal of even a single N-linked glycan can influence the structural integrity and dynamics of the protein that are linked to an enzyme's catalytic proficiency, while indicating that extensive glycosylation protects the enzyme during pathogenesis by protecting it from protease degradation.

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Chorography of blood proteins

Weisel

2023

Journal of Thrombosis and Haemostasis

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Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen

Cited by 5 publications

References 73 publications

Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research

Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research

Impact of N-Glycosylation on Protein Structure and Dynamics Linked to Enzymatic C–H Activation in the M. oryzae Lipoxygenase

Chorography of blood proteins

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