A PUTATIVE SIGNAL PEPTIDASE RECOGNITION SITE AND SEQUENCE IN EUKARYOTIC AND PROKARYOTIC SIGNAL PEPTIDES
A PUTATIVE SIGNAL PEPTIDASE RECOGNITION SITE AND SEQUENCE IN EUKARYOTIC AND PROKARYOTIC SIGNAL PEPTIDES
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DOI：
10.1016/s0022-2836(83)80341-6
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发表时间：
1983-01-01
影响因子：
5.6
通讯作者：
HALVORSON, HO
中科院分区：
文献类型：
--
作者：
PERLMAN, D;HALVORSON, HO
比较了39种原核和真核来源蛋白质的分泌前信号肽。虽然长度和氨基酸组成不同，但不稳定肽共有约1000的疏水核心。12种氨基酸。带正电荷的残基（赖氨酸或精氨酸）通常位于疏水核心之前。核心终止通过带电残基的出现来定义，带电残基是可以诱导β-半乳糖苷酶的残基序列。在多肽中的转折，或潜在α-螺旋或β-延伸股结构。疏水核含有按重量平均计37%亮氨酸：15%丙氨酸：10%缬氨酸：10%苯丙氨酸：7%异亮氨酸加上21%以非随机序列排列的其它疏水氨基酸。在疏水核心（通过其最后一个残基排列）之后，丙氨酸的高度非随机和局部分布在核心之后的最初8个位置内是明显的：图形 **。与这一观察结果相一致，Ala-X-Ala是信号肽酶切割前最常见的序列。信号肽酶识别序列。**图形 **。具有优选的切割位点（附图标记）位于核心序列之后的第6个氨基酸之后。在上述27个加下划线的丙氨酸残基中，22个将作为A或B参与肽酶切割。位置A包括较大的脂肪族氨基酸，亮氨酸、缬氨酸和异亮氨酸，以及已经在B发现的残基（主要是丙氨酸、甘氨酸和丝氨酸）。由于一个优选的切割位点可以从疏水核心的羧基而不是氨基末端排列中辨别出来，因此提出羧基末端向内朝向内质网的内腔，在那里切割被认为发生。该取向与预测的β-通常在核心和切割位点之间发现的转角意味着信号序列的反向发夹插入。所描述的结构特征应有助于鉴定来自DNA序列的假定氨基酸序列中的信号肽和切割位点。
Presecretory signal peptides of 39 proteins from diverse prokaryotic and eukaryotic sources were compared. Although varying in length and amino acid composition, the labile peptides share a hydrophobic core of .apprx. 12 amino acids. A positively charged residue (lysine or arginine) usually precedes the hydrophobic core. Core termination is defined by the occurrence of a charged residue, a sequence of residues which may induce a .beta.-turn in a polypeptide, or an interruption in potential .alpha.-helix or .beta.-extended strand structure. The hydrophobic cores contain, by weight average, 37% leucine: 15% alanine: 10% valine: 10% phenylalanine: 7% isoleucine plus 21% other hydrophobic amino acids arranged in a non-random sequence. Following the hydrophobic cores (aligned by their last residue) a highly non-random and localized distribution of alanine is apparent within the initial 8 positions following the core: .**GRAPHIC**. Coincident with this observation, Ala-X-Ala is the most frequent sequence preceding signal peptidase cleavage. A signal peptidase recognition sequence .**GRAPHIC**. with the preferred cleavage site (.dwnarw.) located after the 6th amino acid following the core sequence is proposed. Of the above 27 underlined alanine residues, 22 would participate as A or B in peptidase cleavage. Position A includes the larger aliphatic amino acids, leucine, valine and isoleucine, as well as the residues already found at B (principally alanine, glycine and serine). Since a preferred cleavage site can be discerned from carboxyl and not amino terminal alignment of the hydrophobic cores it is proposed that the carboxyl ends are oriented inward toward the lumen of the endoplasmic reticulum where cleavage is thought to occur. This orientation coupled with the predicted .beta.-turn typically found between the core and the cleavage site implies reverse hairpin insertion of the signal sequence. The structural features described should help identify signal peptides and cleavage sites in presumptive amino acid sequences derived from DNA sequences.