Structural disorder provides increased adaptability for vesicle trafficking pathways.
Structural disorder provides increased adaptability for vesicle trafficking pathways.
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DOI：
10.1371/journal.pcbi.1003144
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发表时间：
2013
影响因子：
4.3
通讯作者：
Tompa P
中科院分区：
文献类型：
--
作者：
Pietrosemoli N;Pancsa R;Tompa P
囊泡运输系统在真核细胞的细胞器之间以及细胞与其环境之间的通信中起着重要作用。胞吞作用和晚期分泌途径由网格蛋白包被的囊泡介导，而COat蛋白I和II（COPI和COPII）途径代表ER和高尔基体之间的双向交通。尽管基本组织相似，但这三个系统的分子机制、功能和进化特征却大不相同。本研究中，我们整理了人类和酵母的三条主要途径的基本功能蛋白质组，并从结构紊乱的角度对其进行了分析。我们在酵母和人类蛋白质中发现了类似的整体无序内容，证实了这些系统的保守性。大多数功能基团含有高度无序的蛋白质，支持结构紊乱在这些途径中的普遍重要性，尽管其中一些似乎严重依赖于紊乱，而另一些则不是。有趣的是，网格蛋白系统比其他两个，COPI（109%）和COPII（108%）更无序（1023%）。我们发现，这种结构现象增强了固有的可塑性和增加进化适应性的网格蛋白系统，这使它区别于其他两条路线。由于多功能性（兼职）是可塑性和适应性的指标，我们研究了它在囊泡运输蛋白中的流行程度，并将其与结构紊乱相关联。网格蛋白衔接子具有最高的兼职能力，同时还包含最高度无序的成员。获得组织特异性功能的能力也用于接近适应性：网格蛋白途径基因具有编码富含结构紊乱和相互作用位点的蛋白质片段的最组织特异性外显子。总的来说，我们的研究结果证实了结构紊乱在囊泡运输中的普遍重要性，并建议这种结构特性在塑造三种途径的进化适应性差异中发挥重要作用。囊泡运输系统是细胞运输机制中的基础;在每个真核细胞中，各种货物分子通过不同的包被囊泡运输到其特定目的地。网格蛋白包被的囊泡介导内吞作用和晚期分泌途径，而COat蛋白I和II（COPI和COPII）囊泡运输途径负责ER和高尔基体之间的双向运输。尽管这三个系统的基本原理、调控机制和结构特征相似，但它们的分子机制、功能和进化特征却有很大差异。我们从结构无序的角度研究和比较了这三种途径及其基本功能蛋白质组，因为无序的蛋白质区域可以为它们提供各种各样的功能和进化优势。我们发现，结构紊乱的蛋白片段是最丰富的网格蛋白系统，这可能解释了观察到的固有的可塑性，增加适应性和特殊的鲁棒性，这条路线。我们支持我们的假设，通过两个分析蛋白质的多功能性和组织特异性，都是进化适应性的指标。网格蛋白途径蛋白在这两个方面都很突出，它们的无序区域在很大程度上是它们杰出能力的原因。
Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more disordered (∼23%) than the other two, COPI (∼9%) and COPII (∼8%). We show that this structural phenomenon enhances the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of structural disorder in vesicle trafficking and suggest major roles for this structural property in shaping the differences of evolutionary adaptability in the three routes. Vesicle trafficking systems are fundamental among cellular transport mechanisms; various cargo molecules are transported via different coated vesicles to their specific destinations in every eukaryotic cell. Clathrin-coated vesicles mediate endocytosis and the late secretory route, while the COat Protein I and II (COPI and COPII) vesicle trafficking routes are responsible for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar basic principles, regulatory mechanisms and structural features of the three systems, their molecular machinery, functions, and evolutionary characteristics vastly differ. We investigated and compared these three routes and their basic functional protein groups from the structural disorder point of view, since disordered protein regions could provide a broad variety of functional and evolutionary advantages for them. We found that structurally disordered protein segments are most abundant in the clathrin system, which might explain the observed inherent plasticity, increased adaptability and exceptional robustness of this route. We support our hypothesis by two analyses on protein multi-functionality and tissue specificity, both being indicative of evolutionary adaptability. Clathrin pathway proteins stand out in both measures, with their disordered regions being largely responsible for their outstanding capabilities.
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影响因子：
14.9
作者：
Dimmer EC;Huntley RP;Alam-Faruque Y;Sawford T;O'Donovan C;Martin MJ;Bely B;Browne P;Mun Chan W;Eberhardt R;Gardner M;Laiho K;Legge D;Magrane M;Pichler K;Poggioli D;Sehra H;Auchincloss A;Axelsen K;Blatter MC;Boutet E;Braconi-Quintaje S;Breuza L;Bridge A;Coudert E;Estreicher A;Famiglietti L;Ferro-Rojas S;Feuermann M;Gos A;Gruaz-Gumowski N;Hinz U;Hulo C;James J;Jimenez S;Jungo F;Keller G;Lemercier P;Lieberherr D;Masson P;Moinat M;Pedruzzi I;Poux S;Rivoire C;Roechert B;Schneider M;Stutz A;Sundaram S;Tognolli M;Bougueleret L;Argoud-Puy G;Cusin I;Duek-Roggli P;Xenarios I;Apweiler R
通讯作者：
Apweiler R
影响因子：
6.1
作者：
Dyson, H. Jane
通讯作者：
Dyson, H. Jane
影响因子：
64.5
作者：
Fölsch, H;Ohno, H;Mellman, I
通讯作者：
Mellman, I
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
5.8
作者：
Dosztányi, Z;Csizmok, V;Simon, I
通讯作者：
Simon, I