Frangione B, Rosenwasser E, Prelli F, Franklin E C
Biochemistry. 1980 Sep 2;19(18):4304-8. doi: 10.1021/bi00559a024.
The complete sequence of a gamma 3 heavy-chain disease (HCD) protein Wis is presented. The molecule is a dimer of a 289-residue chain linked by 12 disulfide bonds. Protein Wis has an unusual amino terminus, followed by a deletion of most of the VH domain. After a small stretch homologous to the VC joining region, there is a second deletion which ends at the beginning of the quadruplicated hinge. Two carbohydrate groups are linked to Asn-6 and -140. the molecule has an extra interchain disulfide bridge at position 7 in addition to the 11 normally present in the quadruplicated hinge. The previously noted homology to the gamma 1 heavy chain is striking; from positions 224 to 234, protein Wis resembles gamma 1 Nei [Ponstingl, H., & Hilschmann, N. (1976) Hoppe-Seyler's Z. Physiol. Chem. 357, 1571--1604] except for a serine which replaces Asn at position 227. The results, taken together with studies of other immunoglobulin heavy-chain deletion mutants, support the suggestion that the different domains and interdomain regions of human H chains are coded for by different gene segments and that the deleted proteins reflect alterations in the recombination of different genes and/or the splicing of heterogeneous nuclear messenger ribonucleic acid (hn mRNA).
本文展示了γ3重链病（HCD）蛋白Wis的完整序列。该分子是由12个二硫键连接的289个残基链的二聚体。蛋白Wis具有异常的氨基末端，随后是大部分VH结构域的缺失。在一段与VC连接区同源的短序列之后，存在第二个缺失，该缺失在四重铰链区开始处结束。两个糖基与Asn-6和-140相连。除了四重铰链区通常存在的11个二硫键外，该分子在第7位还有一个额外的链间二硫键。先前指出的与γ1重链的同源性非常显著；从第224位到234位，蛋白Wis类似于γ1 Nei [Ponstingl, H., & Hilschmann, N. (1976) Hoppe-Seyler's Z. Physiol. Chem. 357, 1571--1604]，只是在第227位丝氨酸取代了Asn。这些结果与对其他免疫球蛋白重链缺失突变体的研究一起，支持了这样的观点，即人类重链的不同结构域和结构域间区域由不同的基因片段编码，并且缺失的蛋白反映了不同基因重组和/或异质核信使核糖核酸（hn mRNA）剪接的改变。
