Proteolytic and nonproteolytic activation mechanisms result in conformationally and functionally different forms of coagulation factor XIII A

Boris A. Anokhin; William L. Dean; Kerrie A. Smith; Matthew J. Flick; Robert A. S. Ariëns; Helen Philippou; M. Maurer

doi:10.1111/febs.15040

journal article Aug 28, 2019

Proteolytic and nonproteolytic activation mechanisms result in conformationally and functionally different forms of coagulation factor XIII A

Boris A. Anokhin William L. Dean Kerrie A. Smith Matthew J. Flick Robert A. S. Ariëns Helen Philippou M. Maurer

The FEBS Journal Vol. 287 No. 3 pp. 452-464 · Wiley

View at Publisher Save 10.1111/febs.15040

Abstract

Factor XIIIA (FXIIIA) is a transglutaminase that cross‐links intra‐ and extracellular protein substrates. FXIIIA is expressed as an inactive zymogen, and during blood coagulation, it is activated by removal of an activation peptide by the protease thrombin. No such proteolytic FXIIIA activation is known to occur in other tissues or the intracellular form of FXIIIA. For those locations, FXIIIA is assumed instead to undergo activation by Ca2+ ions. Previously, we demonstrated a monomeric state for active FXIIIA. Current analytical ultracentrifugation and kinetic experiments revealed that thrombin‐activated FXIIIA has a higher conformational flexibility and a stronger affinity toward glutamine substrate than does nonproteolytically activated FXIIIA. The proteolytic activation of FXIIIA was further investigated in a context of fibrin clotting. In a series of fibrin cross‐linking assays and scanning electron microscopy studies of plasma clots, the activation rates of FXIIIA V34X variants were correlated with the extent of fibrin cross‐linking and incorporation of nonfibrous protein into the clot. Overall, the results suggest conformational and functional differences between active FXIIIA forms, thus expanding the understanding of FXIIIA function. Those differences may serve as a basis for developing therapeutic strategies to target FXIIIA in different physiological environments.EnzymesFactor XIIIA ( EC 2.3.2.13)

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References

55

[1]

10.1111/j.1538-7836.2010.04070.x

[2]

10.1152/physrev.00016.2010

[3]

10.1055/s-0036-1571341

[4]

10.1152/physrev.00019.2013

[5]

10.1016/j.bone.2017.04.007

[6]

10.1038/cdd.2017.21

[7]

10.1002/jcp.26603

[8]

10.1160/th14-07-0625

[9]

10.1007/s00018-003-2178-9

[10]

10.1111/jth.14348

[11]

10.1016/0003-9861(64)90235-8

[12]

10.1111/jth.12455

[13]

10.1055/s-0038-1653844

[14]

10.1055/s-0038-1651596

[15]

10.1042/bj2670557

[16]

10.1371/journal.pone.0015893

[17]

10.1055/s-0037-1615758

[18]

10.1182/blood-2014-06-583070

[19]

10.1002/jcp.23040

[20]

10.1016/j.bone.2013.11.006

[21]

10.1369/jhc.6a7091.2007

[22]

10.1016/j.matbio.2015.02.001

[23]

10.1016/j.biocel.2008.01.019

[24]

10.1016/j.jbo.2016.06.004

[25]

10.1097/moh.0000000000000445

[26]

10.1182/blood-2014-08-594754

[27]

10.1111/febs.14272

[28]

Modern analytical ultracentrifugation in protein science: A tutorial review

Jacob Lebowitz, Marc S. Lewis, Peter Schuck

Protein Science 10.1110/ps.0207702

[29]

10.1074/jbc.274.32.22862

[30]

Jadhav MA "Screening cleavage of Factor XIII V34X Activation Peptides by thrombin mutants: a strategy for controlling fibrin architecture" Biochem Biophys Acta (2017)

[31]

10.1021/bi00444a027

[32]

10.1161/atvbaha.115.306695

[33]

10.1182/bloodadvances.2017011890

[34]

10.1182/blood-2016-04-712323

[35]

10.1055/s-0038-1648185

[36]

10.1182/blood-2015-09-672303

[37]

10.1016/j.abb.2011.05.009

[38]

10.1021/bi00713a012

[39]

10.1016/j.thromres.2013.02.008

[40]

10.1002/anie.201305133

[41]

10.1371/journal.pone.0160189

[42]

10.1002/9780470122990.ch1

[43]

10.1042/bj1690397

[44]

10.1021/bi00239a014

[45]

10.1055/s-2007-999035

[46]

10.1016/j.bioorg.2014.06.003

[47]

10.1016/s0021-9258(18)99309-9

[48]

10.1021/bi049260

[49]

10.1021/bi700579z

[50]

10.1016/j.bbapap.2006.06.007

Showing 50 of 55 references

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Details

Published: Aug 28, 2019
Vol/Issue: 287(3)
Pages: 452-464
License: View

Authors

B

Boris A. Anokhin

Department of Chemistry University of Louisville KY USA

W

William L. Dean

Brown Cancer Center University of Louisville School of Medicine KY USA; Department of Medicine University of Louisville KY USA; Department of Biochemistry and Molecular Genetics University of Louisville KY USA

K

Kerrie A. Smith

Leeds Thrombosis Collective Department of Discovery and Translational Science Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds UK

M

Matthew J. Flick

Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center OH USA

R

Robert A. S. Ariëns

Leeds Thrombosis Collective Department of Discovery and Translational Science Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds UK

H

Helen Philippou

Leeds Thrombosis Collective Department of Discovery and Translational Science Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds UK

M

M. Maurer

Department of Chemistry University of Louisville KY USA

Funding

National Institutes of Health Award: R01 CA211098

British Heart Foundation Award: PG/08/052/25172

Cite This Article

Boris A. Anokhin, William L. Dean, Kerrie A. Smith, et al. (2019). Proteolytic and nonproteolytic activation mechanisms result in conformationally and functionally different forms of coagulation factor XIII A. The FEBS Journal, 287(3), 452-464. https://doi.org/10.1111/febs.15040

Proteolytic and nonproteolytic activation mechanisms result in conformationally and functionally different forms of coagulation factor XIII A

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