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一种生物活性和免疫反应性较低的新大陆灵长类胰岛素的序列。

Sequence of a New World primate insulin having low biological potency and immunoreactivity.

作者信息

Seino S, Steiner D F, Bell G I

机构信息

Howard Hughes Medical Institute, University of Chicago, IL 60637.

出版信息

Proc Natl Acad Sci U S A. 1987 Nov;84(21):7423-7. doi: 10.1073/pnas.84.21.7423.

DOI:10.1073/pnas.84.21.7423
PMID:3118367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC299308/
Abstract

The organization of the insulin gene of the owl or night monkey (Aotus trivirgatus), a New World primate, is similar to that of the human gene. The sequences of these two genes and flanking regions possess 84.3% homology. An unusual feature of the owl monkey gene is the partial duplication and insertion of a portion of the A-chain coding sequence into the 3' untranslated region. The insulin gene of this primate also lacks a region of tandem repeats that is present in the 5' flanking region of the human and chimpanzee genes. Owl monkey preproinsulin has 85.5% identity with the human insulin precursor and is the most divergent of the primate insulins/preproinsulins yet described. The differences between owl monkey and human preproinsulin include three substitutions in the signal peptide, two in the B chain, seven in the C peptide, and three in the A chain. One of these replacements is the conservative substitution of valine for isoleucine at position A2, an invariant site in all other vertebrate insulins and insulin-like growth factors. The substitutions in owl monkey insulin at B9, B27, A2, A4, and A17 alter its structure so that it has only 20% of the receptor-binding activity and 1% of the affinity with guinea pig anti-porcine insulin antibodies as compared to human insulin.

摘要

新大陆灵长类动物猫头鹰猴(夜猴)的胰岛素基因组织与人类基因相似。这两个基因及其侧翼区域的序列具有84.3%的同源性。猫头鹰猴基因的一个不寻常特征是A链编码序列的一部分部分重复并插入到3'非翻译区。这种灵长类动物的胰岛素基因在人类和黑猩猩基因的5'侧翼区域也缺乏串联重复区域。猫头鹰猴前胰岛素原与人类胰岛素前体有85.5%的一致性,是迄今所描述的灵长类胰岛素/前胰岛素原中差异最大的。猫头鹰猴和人类前胰岛素原之间的差异包括信号肽中有三个替换、B链中有两个、C肽中有七个以及A链中有三个。其中一个替换是在A2位置缬氨酸对异亮氨酸的保守替换,A2在所有其他脊椎动物胰岛素和胰岛素样生长因子中是一个不变位点。猫头鹰猴胰岛素在B9、B27、A2、A4和A17的替换改变了其结构,因此与人类胰岛素相比,它只有20%的受体结合活性和1%与豚鼠抗猪胰岛素抗体的亲和力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5765/299308/4d9c1828064c/pnas00336-0075-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5765/299308/c94cecb3dfda/pnas00336-0074-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5765/299308/4d9c1828064c/pnas00336-0075-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5765/299308/c94cecb3dfda/pnas00336-0074-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5765/299308/4d9c1828064c/pnas00336-0075-a.jpg

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本文引用的文献

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A monomeric insulin from the porcupine (Hystrix cristata), an Old World hystricomorph.一种来自豪猪(帚尾豪猪,一种东半球豪猪亚目动物)的单体胰岛素。
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Guinea pig preproinsulin gene: an evolutionary compromise?豚鼠胰岛素原基因:一种进化上的妥协?
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Use of unpurified synthetic deoxynucleotide primers for rapid dideoxynucleotide chain termination sequencing.使用未纯化的合成脱氧核苷酸引物进行快速双脱氧核苷酸链终止测序。
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