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伴侣蛋白组学,一种研究衰老及相关疾病的新工具。

Chaperonomics, a new tool to study ageing and associated diseases.

作者信息

Brocchieri Luciano, Conway de Macario Everly, Macario Alberto J L

机构信息

University of Florida, College of Medicine, Department of Molecular Genetics and Microbiology, UF Genetics Institute, P.O. Box 103610, Gainesville, FL 32610-3610, USA.

出版信息

Mech Ageing Dev. 2007 Jan;128(1):125-36. doi: 10.1016/j.mad.2006.11.019. Epub 2006 Nov 22.

Abstract

The participation of molecular chaperones in the process of senescence and in the mechanisms of age-related diseases is currently under investigation in many laboratories. However, accurate, complete information about the number and diversity of chaperone genes in any given genome is scarce. Consequently, the results of efforts aimed at elucidating the role of chaperones in ageing and disease are often confusing and contradictory. To remedy this situation, we have developed chaperonomics, including means to identify and characterize chaperone genes and their families applicable to humans and model organisms. The problem is difficult because in eukaryotic organisms chaperones have evolved into complex multi-gene families. For instance, the occurrence of multiple paralogs in a single genome makes it difficult to interpret results if consideration is not given to the fact that similar but distinct chaperone genes can be differentially expressed in separate cellular compartments, tissues, and developmental stages. The availability of complete genome sequences allows implementation of chaperonomics with the purpose of understanding the composition of chaperone families in all cell compartments, their evolutionary and functional relations and, ultimately, their role in pathogenesis. Here, we present a series of concatenated, complementary procedures for identifying, characterizing, and classifying chaperone genes in genomes and for elucidating evolutionary relations and structural features useful in predicting functional properties. We illustrate the procedures with applications to the complex family of hsp70 genes and show that the kind of data obtained can provide a solid basis for future research.

摘要

目前,许多实验室正在研究分子伴侣在衰老过程以及与年龄相关疾病机制中的作用。然而,关于任何给定基因组中伴侣基因的数量和多样性的准确、完整信息却很匮乏。因此,旨在阐明伴侣蛋白在衰老和疾病中作用的研究结果往往令人困惑且相互矛盾。为了改善这种情况,我们开发了伴侣蛋白质组学,包括用于识别和表征适用于人类和模式生物的伴侣基因及其家族的方法。这个问题很棘手,因为在真核生物中,伴侣蛋白已经进化成复杂的多基因家族。例如,如果不考虑相似但不同的伴侣基因可能在不同的细胞区室、组织和发育阶段差异表达这一事实,那么单个基因组中多个旁系同源物的存在就很难解释结果。完整基因组序列的可得性使得实施伴侣蛋白质组学成为可能,其目的是了解所有细胞区室中伴侣蛋白家族的组成、它们的进化和功能关系,以及最终它们在发病机制中的作用。在这里,我们提出了一系列连贯、互补的程序,用于在基因组中识别、表征和分类伴侣基因,以及阐明有助于预测功能特性的进化关系和结构特征。我们通过应用于hsp70基因的复杂家族来说明这些程序,并表明所获得的数据类型可以为未来的研究提供坚实的基础。

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