Colafranceschi Mauro, Papi Massimiliano, Giuliani Alessandro, Amiconi Gino, Colosimo Alfredo
Department of Human Physiology and Pharmacology Vittorio Erspamer, University of Rome, La Sapienza, Rome, Italy.
Pathophysiol Haemost Thromb. 2006;35(6):417-27. doi: 10.1159/000102048.
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.
采用非线性方法——递归定量分析，对野生型以及多个天然存在或模拟的突变体的人纤维蛋白原α-、β-和γ-链中的疏水性模式分布进行了研究。目的是找到区分沉默突变体和病理性突变体的结构基础。由于α-链与其他两条链相比具有独特特征，我们在α-链突变的情况下取得了成功。关于α-链点突变的相关发现如下：(a) 基于递归定量分析对这些突变体的分类与临床分类高度一致，(b) 序列上突变残基的位置比其疏水特征发挥更重要的作用。α-链延伸异构体末端区域（600 - 866个残基）的人工点突变体与第一个（1 - 207）残基的天然出血性突变体聚集在一起。
