Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Natan, Eviatar; Endoh, Tamaki; Haim-Vilmovsky, Liora; Flock, Tilman; Chalancon, Guilhem; Hopper, Jonathan T. S.; Kintses, Bálint; Horváth, Péter; Daruka, Lejla; Fekete, G.; Pál, Csaba; Papp, Balázs; Őszi, Erika; Magyar, Zoltán; Marsh, Joseph A.; Elcock, Adrian H.; Babu, M. Madan; Robinson, Carol V.; Sugimoto, Naoki; Teichmann, Sarah A.

doi:10.1038/s41594-018-0029-5

Cited by 48 publications

(66 citation statements)

References 67 publications

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“…Co-translational assembly in homomeric proteins can also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. Thus, it seems that homomeric protein IDs are enriched toward the C termini of polypeptide chains across diverse proteomes and it has been suggested that this is the result of evolutionary constraints for folding to occur before assembly 38 .…”

Section: Discussionmentioning

confidence: 99%

Co-translation drives the assembly of mammalian nuclear multisubunit complexes

Kamenova

Mukherjee

Conic

et al. 2018

Preprint

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Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding proteins assembling in the same multisubunit complexes are dispersed in the genome of eukaryotes, it is unclear how multisubunit complexes assemble. We show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits but lacking precise architectural details are built cotranslationally. We demonstrate that the dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). Our results indicate that protein translation and complex assembly are linked in building mammalian multisubunit complexes and suggest that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will significantly advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.

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Section: Discussionmentioning

confidence: 99%

Co-translation drives the assembly of mammalian nuclear multisubunit complexes

Kamenova

Mukherjee

Conic

et al. 2018

Preprint

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“…In contrast, the SWI of the full-length sequences has a much stronger correlation with solubility (Spearman's rho = 0.46, P = 2.97 ✕ 10 -19 ; Supplementary Fig S6C). These results suggest that the full-length of sequences contributes to protein solubility, not just surface residues, in which solubility is modulated by cotranslational folding (Natan et al 2018) .…”

Section: Fig 2 Derivation Of the Solubility-weighted Index (Swi) (A)mentioning

confidence: 85%

Solubility-Weighted Index: fast and accurate prediction of protein solubility

Bhandari

Geeleher

Lim

2020

Preprint

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Motivation:Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified. Results:We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli . We have optimised B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the 'Solubility-Weighted Index' (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed 'SoDoPE' (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximising both protein expression and solubility. AvailabilityThe SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS , respectively.

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“…Ordered assembly 263 The time ordering of assembly steps in proteins is integral to the correct assembly of the 264 protein structure. This holds true on many length scales of assembly, with 265 cotranslational protein folding able to induce misassembly [15] all the way up to final 266 quaternary structure as examined here. Experimental methods for devising binding 267 strengths are still being developed [16], with an in silico approach recently introduced 268 focusing on multimeric complexes [17].…”

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confidence: 79%

Evolution of interface binding strengths in simplified model of protein quaternary structure

Leonard

Ahnert

2019

Preprint

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The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new framework for the study of protein self-assembly processes and their evolution.Protein complexes assemble by joining individual proteins together through interacting binding sites. Because of the long time scales of biological evolution, it can be difficult to reconstruct how these interactions change over time. We use simplified representations of proteins to simulate the evolution of these complexes on a computer. In some cases the order in which the complex assembles is crucial. We show that biological evolution increases the strength of interactions that must occur earlier, and decreases the strength of later interactions. Similar knowledge of interactions being preferred to be stronger or weaker can also help to predict the evolutionary ancestry of a complex. While these simulations are not realistic enough to make exact predictions, this general link between ordered pathways in assembly and evolution matches well-established observations that have been made in real protein complexes. This means that our model provides a powerful framework for the study of protein complex assembly and evolution. Introduction 1 Many proteins self-assemble into protein quaternary structures, which fulfill a multitude 2 of functions across a wide range of biological processes [1]. Abstract models trade off 3 the complexity arising from conformations, buried surfaces, cooperative binding, etc., 4 but still retain qualitative realism. A general class of polyomino tile self-assembly 5 models have strong analytic potential while maintaining semblance to protein quatenary 6 structure. 7 The polyomino self-assembly model [2] combines lattice tile self-assembly with a 8 quantification of biological complexity, examining the relationship between genetic 9 description length and phenotypic complexity. The same model was developed and 10 expanded with evolutionary dynamics by Johnston et al. [3], and used to probe general 11 properti...

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Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Cited by 48 publications

References 67 publications

Co-translation drives the assembly of mammalian nuclear multisubunit complexes

Co-translation drives the assembly of mammalian nuclear multisubunit complexes

Solubility-Weighted Index: fast and accurate prediction of protein solubility

Evolution of interface binding strengths in simplified model of protein quaternary structure

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