Heat shock protein 70 family: Multiple sequence comparisons, function, and evolution
Heat shock protein 70 family: Multiple sequence comparisons, function, and evolution
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DOI：
10.1007/pl00006413
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发表时间：
1998-11-01
影响因子：
3.9
通讯作者：
Brocchieri, L
中科院分区：
文献类型：
--
作者：
Karlin, S;Brocchieri, L
热休克蛋白70（HSP 70）作为分子伴侣在蛋白质的折叠和转运过程中起着重要作用。它们在细胞应激的条件下是丰富的。它们在生命的所有领域中高度保守：细菌、真细菌、真核生物和细胞器（线粒体、叶绿体）。使用我们的重复迭代ITERALIGN程序获得了大量这些序列的多重比对（Brocchieri和Karlin 1998）。保护的评估是从进化的角度和功能的影响来解释的。许多古细菌序列（产甲烷菌和嗜盐菌）倾向于与革兰氏阳性序列最佳对齐。这两个组也缺少存在于所有其他HSP 70物种中的特征片段[约25个氨基酸（aa）长]（Gupta和Golding 1993）。我们观察到在所有真核同源物中缺少的约4个aa的第二特征序列，其在所有原核序列中显著对齐。共有序列开发了8组[革兰氏阳性菌、革兰氏阴性菌、单一细菌、线粒体、质体、真核内质网（ER）同种型、真核细胞质同种型]。所有组的一致性比较倾向于比单个序列比较更好地总结比对。全局个体一致性与一致性序列的一致性“匹配”率为87%。全球共识的功能分析确定了一个（新的）高度显着的混合电荷簇的羧基末端的序列，突出了超电荷运行EEDKKRRER（一个字母的aa代码使用）。在共有序列的电荷簇的位置处，单独的革兰氏阳性序列和革兰氏阳性序列包含相应的显著混合电荷簇。相比之下，比对的四个革兰氏阴性变形菌序列不具有电荷簇（即使在5%显著性水平下）。所有真核HSP 70序列都具有类似的电荷簇。引人注目的是，几种真核同工型显示出多个混合电荷簇。这些集群解释与支持数据相关的热休克蛋白70活性，促进伴侣，运输和分泌功能。我们观察到，共识只包含一个单一的色氨酸残基和一个保守的半胱氨酸。这是解释相对于解聚错误折叠蛋白质的目标规则。线粒体HSP 70连接到细菌HSP 70进行了分析，表明从MT-动物/真菌/植物同源物中分离出的锥虫属和利什曼原虫原生动物线粒体（MT）同源物的多系分裂。此外，HSP 70序列的无线粒体溶组织内阿米巴和阴道毛滴虫物种进行了分析。急诊histolytica HSP 70与高等真核细胞胞质序列最相似，与ER序列的比对明显较弱，与所有真细菌、线粒体和叶绿体序列的匹配大大减少。这似乎与E. histolytica而最近失去了线粒体细胞器。T.迷走神经含有两个HSP 70序列，一个类似于MT，第二个类似于真核细胞质序列，表明两种不同的起源。
The heat shook protein 70 kDa sequences (HSP70) are of great importance as molecular chaperones in protein folding and transport. They are abundant under conditions of cellular stress. They are highly conserved in all domains of life: Archaea, eubacteria, eukaryotes, and organelles (mitochondria, chloroplasts), A multiple alignment of a large collection of these sequences was obtained employing our symmetric-iterative ITERALIGN program (Brocchieri and Karlin 1998). Assessments of conservation are interpreted in evolutionary terms and with respect to functional implications. Many archaeal sequences (methanogens and halophiles) tend to align best with the Gram-positive sequences. These two groups also miss a signature segment [about 25 amino acids (aa) long] present in all other HSP70 species (Gupta and Golding 1993), We observed a second signature sequence of about 4 aa absent from all eukaryotic homologues, significantly aligned in all prokaryotic sequences. Consensus sequences were developed for eight groups [Archaea, Gram-positive, proteobacterial Gramnegative, singular bacteria, mitochondria, plastids, eukaryotic endoplasmic reticulum (ER) isoforms, eukaryotic cytoplasmic isoforms]. All group consensus comparisons tend to summarize better the alignments than do the individual sequence comparisons. The global individual consensus "matches" 87% with the consensus of consensuses sequence. A functional analysis of the global consensus identifies a (new) highly significant mixed charge cluster proximal to the carboxyl terminus of the sequence highlighting the hypercharge run EEDKKRRER (one-letter aa code used). The individual Archaea and Gram-positive sequences contain a corresponding significant mixed charge cluster in the location of the charge cluster of the consensus sequence. In contrast, the four Gram-negative proteobacterial sequences of the alignment do not have a charge cluster (even at the 5% significance level). All eukaryotic HSP70 sequences have the analogous charge cluster. Strikingly, several of the eukaryotic isoforms show multiple mixed charged clusters. These clusters were interpreted with supporting data related to HSP70 activity in facilitating chaperone, transport, and secretion function. We observed that the consensus contains only a single tryptophan residue and a single conserved cysteine. This is interpreted with respect to the target rule for disaggregating misfolded proteins. The mitochondrial HSP70 connections to bacterial HSP70 are analyzed, suggesting a polyphyletic split of Trypanosoma and Leishmania protist mitochondrial (Mt) homologues separated from Mt-animal/fungal/plant homologues. Moreover, the HSP70 sequences from the amitochondrial Entamoeba histolytica and Trichomonas vaginalis species were analyzed. The E. histolytica HSP70 is most similar to the higher eukaryotic cytoplasmic sequences, with significantly weaker alignments to ER sequences and much diminished matching to all eubacterial, mitochondrial, and chloroplast sequences. This appears to be at variance with the hypothesis that E. histolytica rather recently lost its mitochondrial organelle. T. vaginalis contains two HSP70 sequences, one Mt-like and the second similar to eukaryotic cytoplasmic sequences suggesting two diverse origins.