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Protein hormone fragmentation in intercellular signaling: hormones as nested information systems
Biology of Reproduction ( IF 3.6 ) Pub Date : 2021-01-10 , DOI: 10.1093/biolre/ioaa234
Kenneth L Campbell 1 , Nurit Haspel 2 , Cassandra Gath 1 , Nuzulul Kurniatash 2 , Indira Nouduri Akkiraju 1 , Naomi Stuffers 1 , Uma Vadher 1
Affiliation  

This study explores the hypothesis that protein hormones are nested information systems in which initial products of gene transcription, and their subsequent protein fragments, before and after secretion and initial target cell action, play additional physiological regulatory roles. The study produced four tools and key results: (1) a problem approach that proceeds, with examples and suggestions for in vivo organismal functional tests for peptide–protein interactions, from proteolytic breakdown prediction to models of hormone fragment modulation of protein–protein binding motifs in unrelated proteins; (2) a catalog of 461 known soluble human protein hormones and their predicted fragmentation patterns; (3) an analysis of the predicted proteolytic patterns of the canonical protein hormone transcripts demonstrating near-universal persistence of 9 ± 7 peptides of 8 ± 8 amino acids even after cleavage with 24 proteases from four protease classes; and (4) a coincidence analysis of the predicted proteolysis locations and the 1939 exon junctions within the transcripts that shows an excess (P < 0.001) of predicted proteolysis within 10 residues, especially at the exonal junction (P < 0.01). It appears all protein hormone transcripts generate multiple fragments the size of peptide hormones or protein–protein binding domains that may alter intracellular or extracellular functions by acting as modulators of metabolic enzymes, transduction factors, protein binding proteins, or hormone receptors. High proteolytic frequency at exonal junctions suggests proteolysis has evolved, as a complement to gene exon fusion, to extract structures or functions within single exons or protein segments to simplify the genome by discarding archaic one-exon genes.

中文翻译:

细胞间信号中的蛋白质激素片段化:激素作为嵌套信息系统

本研究探讨了蛋白质激素是嵌套信息系统的假设,其中基因转录的初始产物及其随后的蛋白质片段,在分泌和初始靶细胞作用之前和之后,发挥额外的生理调节作用。该研究产生了四种工具和关键结果:(1) 提出了一种问题方法,其中包括对肽-蛋白质相互作用的体内有机体功能测试的示例和建议,从蛋白水解分解预测到蛋白质-蛋白质结合基序的激素片段调节模型在不相关的蛋白质中;(2) 461 种已知可溶性人类蛋白质激素的目录及其预测的碎片模式;(3) 对典型蛋白质激素转录物的预测蛋白水解模式的分析表明,即使在用来自四种蛋白酶类的 24 种蛋白酶切割后,9 ± 7 个 8 ± 8 个氨基酸的肽也几乎普遍存在;(4) 预测的蛋白水解位置和转录本内的 1939 个外显子连接的一致性分析,显示 10 个残基内预测的蛋白水解过量 (P < 0.001),尤其是在外显子连接处 (P < 0.01)。似乎所有蛋白质激素转录物都会产生多个肽激素大小的片段或蛋白质-蛋白质结合结构域,这些片段可能通过充当代谢酶、转导因子、蛋白质结合蛋白或激素受体的调节剂来改变细胞内或细胞外功能。
更新日期:2021-01-10
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