Nagano Celso S, Debray Henri, Nascimento Kyria S, Pinto Vicente P T, Cavada Benildo S, Saker-Sampaio Silvana, Farias Wladimir R L, Sampaio Alexandre H, Calvete Juan J
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, E-46010 Valencia, Spain.
Protein Sci. 2005 Aug;14(8):2167-76. doi: 10.1110/ps.051498505.
HCA and HML represent lectins isolated from the red marine algae Hypnea cervicornis and Hypnea musciformis, respectively. Hemagglutination inhibition assays suggest that HML binds GalNAc/Gal substituted with a neutral sugar through 1-3, 1-4, or 1-2 linkages in O-linked mucin-type glycans, and Fuc(alpha1-6)GlcNAc of N-linked glycoproteins. The specificity of HCA includes the epitopes recognized by HML, although the glycoproteins inhibited distinctly HML and HCA. The agglutinating activity of HCA was inhibited by GalNAc, highlighting the different fine sugar epitope-recognizing specificity of each algal lectin. The primary structures of HCA (9193+/-3 Da) and HML (9357+/-1 Da) were determined by Edman degradation and tandem mass spectrometry of the N-terminally blocked fragments. Both lectins consist of a mixture of a 90-residue polypeptide containing seven intrachain disulfide bonds and two disulfide-bonded subunits generated by cleavage at the bond T50-E51 (HCA) and R50-E51 (HML). The amino acid sequences of HCA and HML display 55% sequence identity (80% similarity) between themselves, but do not show discernible sequence and cysteine spacing pattern similarities with any other known protein structure, indicating that HCA and HML belong to a novel lectin family. Alignment of the amino acid sequence of the two lectins revealed the existence of internal domain duplication, with residues 1-47 and 48-90 corresponding to the N- and C-terminal domains, respectively. The six conserved cysteines in each domain may form three intrachain cysteine linkages, and the unique cysteine residues of the N-terminal (Cys46) and the C-terminal (Cys71) domains may form an intersubunit disulfide bond.
HCA和HML分别代表从红藻角叉菜(Hypnea cervicornis)和绳藻(Hypnea musciformis)中分离出的凝集素。血凝抑制试验表明,HML通过O-连接粘蛋白型聚糖中1-3、1-4或1-2连接的中性糖取代的GalNAc/Gal以及N-连接糖蛋白的Fuc(α1-6)GlcNAc结合。HCA的特异性包括HML识别的表位,尽管糖蛋白对HML和HCA的抑制作用明显不同。GalNAc抑制了HCA的凝集活性,突出了每种藻类凝集素不同的精细糖表位识别特异性。通过对N端封闭片段进行埃德曼降解和串联质谱法测定了HCA(9193±3 Da)和HML(9357±1 Da)的一级结构。两种凝集素均由含有七个链内二硫键的90个残基多肽混合物以及在T50-E51键(HCA)和R50-E51键(HML)处裂解产生的两个二硫键连接的亚基组成。HCA和HML的氨基酸序列彼此之间显示出55%的序列同一性(80%的相似性),但与任何其他已知蛋白质结构均未显示出可辨别的序列和半胱氨酸间隔模式相似性,表明HCA和HML属于一个新的凝集素家族。两种凝集素氨基酸序列的比对揭示了内部结构域重复的存在,其中1-47位残基和48-9位残基分别对应于N端和C端结构域。每个结构域中的六个保守半胱氨酸可能形成三个链内半胱氨酸连接,N端(Cys46)和C端(Cys71)结构域的独特半胱氨酸残基可能形成亚基间二硫键。