Effects of Introducing Fibrinogen Aα Character into the Factor XIII Activation Peptide Segment

Jadhav, Madhavi A.; Isetti, Giulia; Trumbo, Toni A.; Maurer, Muriel C.

doi:10.1021/bi902127u

Cited by 4 publications

(4 citation statements)

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“…Finally, selective changes in the FXIII activation peptide sequence, may give back FXIII species with increased activation rates potentially useful in designing and projecting of recombinant FXIIIA molecules [120].…”

Section: Novel Pharmacogenetics Aspects Of Fxiiia Genementioning

confidence: 99%

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics

Gemmati

Vigliano²,

Burini³

et al. 2016

CPD

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Factor XIII (FXIII) is a key molecule in the field of blood coagulation and in the last decades it has weakened attention within the field of angiogenesis and tissue repair. FXIII positively influences wound healing in several tissues by exerting multiple plasma and cellular functions. In the field of haemostasis, FXIII cross-links the neo formed fibrin fibers and supports platelet adhesion to the damaged sub-endothelium warranting a solid architecture. In addition, the pro-angiogenic functions of FXIII are directed by the interaction of vascular endothelial growth factor receptor 2 (VEGFR2) and the integrin αVβ3, on the cell membrane, favouring an important step in the formation of granulation tissue at the wound site for optimal tissue healing. Conversely, the same mechanisms could lead to undesired increased neovascularisation, for example in inflammatory bowel disease or in the retinal degenerative pathologies. The classical symptoms of FXIII deficiency span from intracranial haemorrhage to delay bleeding or the staying of chronic wounds in the skin including impaired mucosal healing. In this view, FXIII bridges primary haemostasis, coagulation and definite tissue healing. Another important recently discovered function ascribed to FXIII is its ability to limit bacterial spreading from the lesion by incorporating specific macromolecules addressed to cellular infiltration, favouring in turn cell migration and survival, as observed also in fibrin-heart cultures for stem cell recruitment. In the field of the novel prognostic biomarkers, the monitoring of the residual circulating FXIII level during acute myocardial infarction has been considered predictive of the post-myocardial infarction healing. Accordingly, adequate FXIII levels can drive and predict the prognosis of complex diseases and the outcome of the associated therapies or interventions. In addition, peculiar pharmacogenetics aspects of the FXIII gene are of extraordinary interest. The present review accounts for the recognized role of FXIII in the healing process and gives some examples on how to use it as prognostic biological/ molecular marker or as potential tailored therapeutic molecule in complex diseases.

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Section: Novel Pharmacogenetics Aspects Of Fxiiia Genementioning

confidence: 99%

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics

Gemmati

Vigliano²,

Burini³

et al. 2016

CPD

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“…Since then, the effects of individual amino acids of AP-FXIII around the thrombin cleavage site on protein conformation, interactions with thrombin and efficiency of FXIII activation have been studied. 10,[25][26][27] However, the role of Pro36, an amino acid with unique properties which is located just one position upstream from the cleavage site, has never been investigated using mutant variants. Duval et al have recently attempted to express a Pro36Ala variant which failed to transform and express in Escherichia coli.…”

Section: Discussionmentioning

confidence: 99%

Proline 36 of the Factor XIII Activation Peptide Plays a Crucial Role in Substrate Recognition and Zymogen Activation

Billur

Maurer

et al. 2018

Thromb Haemost

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The activation peptide of blood coagulation factor XIII (AP-FXIII) has important functions in stabilising the FXIII-A2 dimer and regulating FXIII activation. Contributions of many of its 37 amino acids to these functions have been described. However, the role of proline 36, which is adjacent to the thrombin cleavage site at Arg37, has not yet been studied in detail. We approached this question when we came across a patient with congenital FXIII deficiency in whom we detected a novel Pro36Ser mutation. We expressed the mutant FXIII-A Pro36Ser protein in CHO cells and found that this mutation does not influence FXIII-A expression but significantly inhibits proteolytic activation by thrombin. The enzymatic transglutaminase activity is not affected as it can be induced in the presence of high Ca2+ concentrations. We performed Nuclear Magnetic Resonance (NMR) analysis to investigate AP-FXIII-thrombin interactions, which showed that the mutant Ser36 peptide binds less well to the thrombin surface than the native Pro36 peptide. The Arg37 at the P1 position still makes strong interactions with the active site cleft but the P4-P2 residues (34VVS36) appear to be less well positioned to contact the neighbouring thrombin active site region. In conclusion, we have characterised a novel mutation in AP-FXIII representing only the fourth case of the rare FXIII-A type II deficiency. This case served as a perfect in vivo model to shed light on the crucial role of Pro36 in the proteolytic activation of FXIII-A. Our results contribute to the understanding of structure-function relationship in FXIII.

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“…BGK-FBG-4150 Sensor mainly used for strain measurement on the frame construction, especially in harsh environments like severe storms, thunder and dust [8][9][10]. The fiber optic sensor is welded to the crane computed position.…”

Section: Introduction: Research Purposementioning

confidence: 99%

Optimal FBG Sensor Installation Process for Crane SHM System

Wang¹,

Wang

Huang³

et al. 2013

AMM

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In order to improve the accuracy of measurement results, we should do our best to reduce the optical loss while welding FBG Sensors and adopt appropriate bonding technology. Taking simple tools and suitable approach can also achieve good result. We take three steps while welding FBG sensors, the steps are manufacture end face, welding, and heat shrinkable. Manufacturing end face of a fiber is the key step among them. It is important to adopt the sequence diagonal welding method and use a damp cloth to cool the other parts of the sensor while welding which can increase the accuracy of measurement. Use pen-made red light to check the fiber joints.

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Effects of Introducing Fibrinogen Aα Character into the Factor XIII Activation Peptide Segment

Cited by 4 publications

References 50 publications

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics

Coagulation Factor XIIIA (F13A1): Novel Perspectives in Treatment and Pharmacogenetics

Proline 36 of the Factor XIII Activation Peptide Plays a Crucial Role in Substrate Recognition and Zymogen Activation

Optimal FBG Sensor Installation Process for Crane SHM System

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