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小鼠Cμ重链免疫球蛋白基因片段包含三个分隔结构域的间隔序列。

Mouse Cmu heavy chain immunoglobulin gene segment contains three intervening sequences separating domains.

作者信息

Calame K, Rogers J, Early P, Davis M, Livant D, Wall R, Hood L

出版信息

Nature. 1980 Apr 3;284(5755):452-5. doi: 10.1038/284452a0.

DOI:10.1038/284452a0
PMID:6767197
Abstract

The IgM molecule is composed of subunits made up of two light chain and two heavy chain (mu) polypeptides. The mu chain is encoded by several gene segments--variable (V), joining (J) and constant (Cmu). The Cmu gene segment is of particular interest for several reasons. First, the mu chain must exist in two very different environments--as an integral membrane protein in receptor IgM molecules (micrometer) and as soluble serum protein in IgM molecules into the blood (mus). Second, the Cmu region in mus is composed of four homology units or domains (Cmu1, Cmu2, Cmu3 and Cmu4) of approximately 110 amino acid residues plus a C-terminal tail of 19 residues. We asked two questions concerning the organisation of the Cmu gene segment. (1) Are the homology units separated by intervening DNA sequences as has been reported for alpha (ref. 5), gamma 1 (ref. 6) and gamma 2b (ref. 7) heavy chain genes? (2) Is the C-terminal tail separated from the Cmu4 domain by an intervening DNA sequence? If so, DNA rearrangements or RNA splicing could generate hydrophilic and hydrophobic C-terminal tails for the mus and micrometer polypeptides, respectively. We demonstrate here that intervening DNA sequences separate each of the four coding regions for Cmu domains, and that the coding regions for the Cmu4 domains and the C-terminal tail are directly contiguous.

摘要

IgM分子由亚基组成,这些亚基由两条轻链和两条重链(μ)多肽构成。μ链由几个基因片段编码,即可变区(V)、连接区(J)和恒定区(Cμ)。Cμ基因片段因多种原因而备受关注。首先,μ链必须存在于两种截然不同的环境中:作为受体IgM分子(μm)中的整合膜蛋白,以及作为血液中IgM分子的可溶性血清蛋白(μs)。其次,μs中的Cμ区域由四个同源单位或结构域(Cμ1、Cμ2、Cμ3和Cμ4)组成,每个结构域约有110个氨基酸残基,外加一个19个残基的C末端尾巴。我们针对Cμ基因片段的组织提出了两个问题。(1)同源单位是否像已报道的α(参考文献5)、γ1(参考文献6)和γ2b(参考文献7)重链基因那样被间隔DNA序列隔开?(2)C末端尾巴是否通过间隔DNA序列与Cμ4结构域分开?如果是这样,DNA重排或RNA剪接可能分别为μs和μm多肽产生亲水和疏水的C末端尾巴。我们在此证明,间隔DNA序列将Cμ结构域的四个编码区域彼此隔开,并且Cμ4结构域和C末端尾巴的编码区域直接相邻。

相似文献

1
Mouse Cmu heavy chain immunoglobulin gene segment contains three intervening sequences separating domains.小鼠Cμ重链免疫球蛋白基因片段包含三个分隔结构域的间隔序列。
Nature. 1980 Apr 3;284(5755):452-5. doi: 10.1038/284452a0.
2
Nucleotide sequence of the constant region of a chicken mu heavy chain immunoglobulin mRNA.鸡μ重链免疫球蛋白mRNA恒定区的核苷酸序列。
Nucleic Acids Res. 1983 Aug 25;11(16):5381-9. doi: 10.1093/nar/11.16.5381.
3
Intervening sequences divide the gene for the constant region of mouse immunoglobulin mu chains into segments, each encoding a domain.间隔序列将小鼠免疫球蛋白μ链恒定区的基因分割成多个片段,每个片段编码一个结构域。
Proc Natl Acad Sci U S A. 1980 Jan;77(1):554-8. doi: 10.1073/pnas.77.1.554.
4
An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH.免疫球蛋白重链可变区基因由三段DNA片段组成:VH、D和JH。
Cell. 1980 Apr;19(4):981-92. doi: 10.1016/0092-8674(80)90089-6.
5
Recombination events near the immunoglobulin Cmu gene join variable and constant region genes, switch heavy-chain expression, or inactivate the locus.免疫球蛋白Cμ基因附近的重组事件会连接可变区和恒定区基因、转换重链表达或使该基因座失活。
Biochemistry. 1981 Apr 28;20(9):2662-71. doi: 10.1021/bi00512a047.
6
Mapping of heavy chain genes for mouse immunoglobulins M and D.小鼠免疫球蛋白M和D重链基因的图谱绘制
Science. 1980 Sep 19;209(4463):1348-53. doi: 10.1126/science.6774414.
7
Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain.两个具有不同3'末端的mRNA编码免疫球蛋白μ链的膜结合形式和分泌形式。
Cell. 1980 Jun;20(2):303-12. doi: 10.1016/0092-8674(80)90616-9.
8
Exon shuffling generates an immunoglobulin heavy chain gene.外显子改组产生免疫球蛋白重链基因。
Proc Natl Acad Sci U S A. 1980 Apr;77(4):2138-42. doi: 10.1073/pnas.77.4.2138.
9
Nucleotide sequence of immunoglobulin heavy chain joining segments between translocated VH and mu constant regions genes.易位的VH基因和μ恒定区基因之间免疫球蛋白重链连接片段的核苷酸序列。
Proc Natl Acad Sci U S A. 1980 Jun;77(6):3630-4. doi: 10.1073/pnas.77.6.3630.
10
Phylogenetic conservation of immunoglobulin heavy chains: direct comparison of hamster and mouse Cmu genes.免疫球蛋白重链的系统发育保守性:仓鼠和小鼠Cμ基因的直接比较。
Nucleic Acids Res. 1985 Aug 12;13(15):5611-28. doi: 10.1093/nar/13.15.5611.

引用本文的文献

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Nat Rev Urol. 2020 Apr;17(4):201-213. doi: 10.1038/s41585-020-0296-x. Epub 2020 Mar 10.
2
How antibodies fold.抗体如何折叠。
Trends Biochem Sci. 2010 Apr;35(4):189-98. doi: 10.1016/j.tibs.2009.11.005. Epub 2009 Dec 21.
3
Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells.转染至淋巴细胞中的免疫球蛋白重链基因的表达与调控
EMBO J. 1983;2(8):1373-8. doi: 10.1002/j.1460-2075.1983.tb01594.x.
4
Identification of an H-2Kb-related molecule by molecular cloning.通过分子克隆鉴定一种与H-2Kb相关的分子。
Immunogenetics. 1981;14(5):383-92. doi: 10.1007/BF00373318.
5
A catalogue of splice junction sequences.剪接连接序列目录。
Nucleic Acids Res. 1982 Jan 22;10(2):459-72. doi: 10.1093/nar/10.2.459.
6
Biosynthesis and structure of membrane and secretory immunoglobulins.膜免疫球蛋白和分泌型免疫球蛋白的生物合成与结构
Mol Cell Biochem. 1982 Aug 20;47(1):11-22. doi: 10.1007/BF00241561.
7
Immunoglobulin heavy chain genes: demethylation accompanies class switching.免疫球蛋白重链基因:去甲基化伴随类别转换。
Proc Natl Acad Sci U S A. 1981 Dec;78(12):7497-501. doi: 10.1073/pnas.78.12.7497.
8
A general function of noncoding polynucleotide sequences. Mass binding of transconformational proteins.非编码多核苷酸序列的一般功能。转构象蛋白的大量结合。
Mol Biol Rep. 1981 May 22;7(1-3):149-58. doi: 10.1007/BF00778746.
9
Primary structure of the Fc region of human immunoglobulin D: implications for evolutionary origin and biological function.人免疫球蛋白D的Fc区一级结构:对进化起源和生物学功能的启示
Proc Natl Acad Sci U S A. 1981 Jan;78(1):504-8. doi: 10.1073/pnas.78.1.504.
10
Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development.免疫球蛋白Cμ基因的转录本在淋巴细胞发育过程中结构和剪接方式存在差异。
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7400-4. doi: 10.1073/pnas.77.12.7400.