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人类与海豚的 TRB 基因座比较:从序列到 α/β 异二聚体结构

The T Cell Receptor (TRB) Locus in : From Sequence to Structure of the Alpha/Beta Heterodimer in the Human/Dolphin Comparison.

机构信息

Department of Biology, University of Bari, "Aldo Moro", 70124 Bari, Italy.

IMGT®, the international ImMunoGeneTics information system®, Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Institut de Génétique Humaine (IGH), 34000 Montpellier, France.

出版信息

Genes (Basel). 2021 Apr 14;12(4):571. doi: 10.3390/genes12040571.

DOI:10.3390/genes12040571
PMID:33919966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8070946/
Abstract

The bottlenose dolphin () belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary, and expression study of T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3' end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the complementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH.

摘要

宽吻海豚()属于偶蹄目,与其他鲸目动物一样,代表了哺乳动物对水生环境最成功的适应。在这里,我们报告了一个关于 T 细胞受体 β(TRB)基因的基因组、进化和表达研究。尽管海豚 TRB 基因座的组织与其他偶蹄目物种相似,具有三个串联的 D-J-C 簇位于其 3'端,但由于缺乏重复序列和缺失序列导致总长度减少,其独特性在于其独特性。这些缺失序列极大地减少了种系 TRBV 基因的数量。我们分析了来自两个对象的相关成熟转录物。由于从两个样本之一的外周血中同时获得了重组的 T 细胞受体 α(TRA)和 TRB cDNA,并且进行了人与海豚氨基酸多序列比对,因此我们可以计算出与主要组织相容性复合体 I(MH1)蛋白结合的 alpha/beta 异二聚体在蛋白质界面上的最可能相互作用。根据海豚可变 V-alpha 和 beta 结构域的 IMGT 编号(CDR-IMGT),鉴定出位于互补决定区(CDR)的相互作用氨基酸。根据比较模型化,在人与海豚 MH1 凹槽(G)结构域和 T 细胞受体(TR)V 结构域之间的原子对接触位点分析证实了海豚 TR/pMH 的结构保守性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/b9e94acc3f5b/genes-12-00571-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/a2975396a312/genes-12-00571-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/b6ed78899f58/genes-12-00571-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/f4823f26112d/genes-12-00571-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/6e5a03a7c5cd/genes-12-00571-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/8f67ea14d44b/genes-12-00571-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/6d19673c1a99/genes-12-00571-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/0da27ea8efb6/genes-12-00571-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/985b2ad826cc/genes-12-00571-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/4615b6705625/genes-12-00571-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/b9e94acc3f5b/genes-12-00571-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/a2975396a312/genes-12-00571-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/b6ed78899f58/genes-12-00571-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/f4823f26112d/genes-12-00571-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/6e5a03a7c5cd/genes-12-00571-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/8f67ea14d44b/genes-12-00571-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/6d19673c1a99/genes-12-00571-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/0da27ea8efb6/genes-12-00571-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/985b2ad826cc/genes-12-00571-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/4615b6705625/genes-12-00571-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1749/8070946/b9e94acc3f5b/genes-12-00571-g010.jpg

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