Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins.
Early Bioinformatic Implication of Triacidic Amino Acid Motifs in Autophagy-Dependent Unconventional Secretion of Mammalian Proteins.
复制标题
DOI：
10.3389/fcell.2022.863825
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
几种蛋白质分泌到细胞外，在许多情况下，它们可以通过特征信号肽识别。然而，越来越多的研究指出了“非常规”分泌的证据，其中可能在饥饿条件下分泌没有迄今未知信号的蛋白质。在这项工作中，我们分析了一组202 RNA结合哺乳动物蛋白，其非常规分泌最近已经建立。对由LC3介导分泌的这些蛋白质的分析，据我们所知最大的非常规分泌数据集，鉴定了KKX基序以及三酸氨基酸基序在非常规分泌中的作用，后者是最近涉及的二元酸氨基酸基序的延伸。进一步的数据分析发展了一个假设的序列或结构接近的三酸或KKX基序的LC 3相互作用区，和磷酸化的氨基酸，如丝氨酸作为一个统计学上显着的功能，这些非常规分泌的蛋白质。这一假设，虽然需要在挑战这些方面的具体细节的实验中得到验证，但似乎是定义什么可能是非常规蛋白质分泌的合理信号的早期步骤之一。
Several proteins are secreted outside the cell, and in many cases, they may be identified by a characteristic signal peptide. However, more and more studies point to the evidence for an “unconventional” secretion, where proteins without a hitherto unknown signal are secreted, possibly in conditions of starvation. In this work, we analyse a set of 202 RNA binding mammalian proteins, whose unconventional secretion has recently been established. Analysis of these proteins secreted by LC3 mediation, the largest unconventionally secreted dataset to our knowledge, identifies the role of KKX motif as well as triacidic amino acid motif in unconventional secretion, the latter being an extension of the recent implicated diacidic amino acid motif. Further data analysis evolves a hypothesis on the sequence or structural proximity of the triacidic or KKX motifs to the LC3 interacting region, and a phosphorylatable amino acid such as serine as a statistically significant feature among these unconventionally secreted proteins. This hypothesis, although needs to be validated in experiments that challenge the specific details of each of these aspects, appears to be one of the early steps in defining what may be a plausible signal for unconventional protein secretion.