Interactions between factor XIII and the αC region of fibrinogen

Kerrie A. Smith, Penelope J. Adamson, Richard J. Pease, Jane M. Brown, Anthony J. Balmforth, Paul A. Cordell, Robert A.S. Ariëns, Helen Philippou, Peter J. Grant

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49 Citations (Scopus)


Fibrinogen αC residues 242-424 have been shown to have a major regulatory role in the activation of factor XIII-A2B2 (FXIII-A2B2); however, the interactions underpinning this enhancing effect have not been determined. Here, we have characterized the binding of recombinant (r)FXIII-A subunit and FXIII-A2B2 with fibrin(ogen) and fibrin αC residues 233-425. 

Using recombinant truncations of the fibrin αC region 233-425 and surface plasmon resonance, we found that activated rFXIII-A bound αC 233-425 (Kd of 2.35 ± 0.09μM) which was further localized to αC 389-403. Site-directed mutagenesis of this region highlighted Glu396 as a key residue for binding of activated rFXIII-A. The interaction was specific for activated rFXIII-A and depended on the calcium-induced conformational change known to occur in rFXIII-A during activation. Furthermore, nonactivated FXIII-A 2B2, thrombin-cleaved FXIII-A2B2, and activated FXIII-A2B2 each bound fibrin(ogen) and specifically αC region 371-425 with high affinity (Kd < 35nM and Kd < 31nM, respectively), showing for the first time the potential involvement of the αC region in binding to FXIII-A 2B2. These results suggest that in addition to fibrinogen γ′ chain binding, the fibrin αC region also provides a platform for the binding of FXIII-A2B2 and FXIII-A subunit.

Original languageEnglish
Pages (from-to)3460-3468
Number of pages9
Issue number12
Publication statusPublished - 24 Mar 2011
Externally publishedYes


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