Simulated point mutations in the Aalpha-chain of human fibrinogen support a role of the alphaC domain in the stabilization of fibrin gel.
The hydrophobicity pattern distribution in the Aalpha-, Bbeta- and gamma-chains of human fibrinogen has been studied by a nonlinear method, recurrence quantification analysis, in the wild type and in a number of naturally occurring or simulated mutants. The aim was to find a structural basis for distinguishing between silent and pathological mutants. We were successful in the case of mutations on the Aalpha-chain, thanks to the peculiar features of this chain as compared to the other two. Relevant findings concerning the point mutants of the Aalpha-chain are the following: (a) the recurrence quantification analysis-based classification of such mutants is in good agreement with the clinical classification, and (b) the location of the mutated residue on the sequence plays a more relevant role than its hydrophobic features. Artificial point mutants in the terminal zone (600-866 residues) of the extended isoform of the Aalpha-chain cluster together with the natural hemorrhagic mutants of the first (1-207) residues.
Colafranceschi
Mauro
M
Department of Human Physiology and Pharmacology Vittorio Erspamer, University of Rome, La Sapienza, Rome, Italy.
Papi
Massimiliano
M
Giuliani
Alessandro
A
Amiconi
Gino
G
Colosimo
Alfredo
A
D005337:Fibrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005782:Gels; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D017354:Point Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics
D005782:Gels; C464794:fibrinogen Aalpha; D005337:Fibrin; D005340:Fibrinogen