Morabito M A, Moczydlowski E
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2478-82. doi: 10.1073/pnas.91.7.2478.
Plasma and tissue of certain vertebrates contain a protein called saxiphilin that specifically binds the neurotoxin saxitoxin with nanomolar affinity. We describe the isolation of a cDNA clone of saxiphilin from liver of the North American bullfrog (Rana catesbeiana). The cDNA sequence encodes a protein that is evolutionarily related to members of the transferrin family of Fe(3+)-binding proteins. Pairwise sequence alignment of saxiphilin with various transferrins reveals amino acid identity as high as 51% and predicts 14 disulfide bonds that are highly conserved. The larger size of saxiphilin (91 kDa) versus serum transferrin (approximately 78 kDa) is primarily due to a unique insertion of 144 residues. This insertion contains a 49-residue domain classified as a type 1 repetitive element of thyroglobulin, which is shared by a variety of membrane, secreted, and extracellular matrix proteins. Saxiphilin also differs from transferrins in 9 of 10 highly conserved amino acids in the two homologous Fe3+/HCO3-binding sites of transferrin. Identification of saxiphilin implies that transferrin-like proteins comprise a diverse superfamily with functions other than iron binding.
某些脊椎动物的血浆和组织中含有一种名为石房蛤毒素结合蛋白的蛋白质，它能以纳摩尔亲和力特异性结合神经毒素石房蛤毒素。我们描述了从北美牛蛙（牛蛙）肝脏中分离石房蛤毒素结合蛋白的cDNA克隆。该cDNA序列编码一种与铁（3 +）结合蛋白转铁蛋白家族成员在进化上相关的蛋白质。石房蛤毒素结合蛋白与各种转铁蛋白的成对序列比对显示氨基酸同一性高达51%，并预测有14个高度保守的二硫键。石房蛤毒素结合蛋白（91 kDa）比血清转铁蛋白（约78 kDa）更大，主要是由于一个独特的144个残基的插入。这个插入包含一个49个残基的结构域，被归类为甲状腺球蛋白的1型重复元件，它存在于多种膜蛋白、分泌蛋白和细胞外基质蛋白中。石房蛤毒素结合蛋白在转铁蛋白两个同源的铁3 + /碳酸氢根结合位点的10个高度保守氨基酸中的9个也与转铁蛋白不同。石房蛤毒素结合蛋白的鉴定意味着类似转铁蛋白的蛋白质构成了一个具有除铁结合以外功能的多样化超家族。
