On the segregation of protein ionic residues by charge type

Parker, Michael S.; Balasubramaniam, Ambikaipakan; Parker, Steven L.

doi:10.1007/s00726-012-1418-4

Cited by 6 publications

(4 citation statements)

References 92 publications

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“…Moreover, metazoan cytosolic ribosomes acquired novel expansion segments (ES) logarithmically over the past two billion years as compared to archaeal and bacterial ribosomes [ 95 , 96 ]. Metazoan RPs have also diversified, increased in number, and in parts diverged [ 97 , 98 , 99 , 100 , 101 ]. Thus, it is likely that the availability of novel rRNA expansion segments and the diversification of RPs enhances promiscuous binding of multiple RP or RP paralog copies per ribosomal particle in metazoans and specially also in plant ribosomes.…”

Section: Discussionmentioning

confidence: 99%

Spatially Enriched Paralog Rearrangements Argue Functionally Diverse Ribosomes Arise during Cold Acclimation in Arabidopsis

Martinez‐Seidel

Beine-Golovchuk

Hsieh

et al. 2021

IJMS

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Ribosome biogenesis is essential for plants to successfully acclimate to low temperature. Without dedicated steps supervising the 60S large subunits (LSUs) maturation in the cytosol, e.g., Rei-like (REIL) factors, plants fail to accumulate dry weight and fail to grow at suboptimal low temperatures. Around REIL, the final 60S cytosolic maturation steps include proofreading and assembly of functional ribosomal centers such as the polypeptide exit tunnel and the P-Stalk, respectively. In consequence, these ribosomal substructures and their assembly, especially during low temperatures, might be changed and provoke the need for dedicated quality controls. To test this, we blocked ribosome maturation during cold acclimation using two independent reil double mutant genotypes and tested changes in their ribosomal proteomes. Additionally, we normalized our mutant datasets using as a blank the cold responsiveness of a wild-type Arabidopsis genotype. This allowed us to neglect any reil-specific effects that may happen due to the presence or absence of the factor during LSU cytosolic maturation, thus allowing us to test for cold-induced changes that happen in the early nucleolar biogenesis. As a result, we report that cold acclimation triggers a reprogramming in the structural ribosomal proteome. The reprogramming alters the abundance of specific RP families and/or paralogs in non-translational LSU and translational polysome fractions, a phenomenon known as substoichiometry. Next, we tested whether the cold-substoichiometry was spatially confined to specific regions of the complex. In terms of RP proteoforms, we report that remodeling of ribosomes after a cold stimulus is significantly constrained to the polypeptide exit tunnel (PET), i.e., REIL factor binding and functional site. In terms of RP transcripts, cold acclimation induces changes in RP families or paralogs that are significantly constrained to the P-Stalk and the ribosomal head. The three modulated substructures represent possible targets of mechanisms that may constrain translation by controlled ribosome heterogeneity. We propose that non-random ribosome heterogeneity controlled by specialized biogenesis mechanisms may contribute to a preferential or ultimately even rigorous selection of transcripts needed for rapid proteome shifts and successful acclimation.

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Section: Discussionmentioning

confidence: 99%

Spatially Enriched Paralog Rearrangements Argue Functionally Diverse Ribosomes Arise during Cold Acclimation in Arabidopsis

Martinez‐Seidel

Beine-Golovchuk

Hsieh

et al. 2021

IJMS

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“…From an evolutionary perspective, both networks should be conserved since the main rProteome acquisitions are shared [ 12 ]. An exception is that higher metazoans (except plants) share an increase of basic LSU rProtein components as compared to lower eukaryotes [ 14 ]. Importantly, in such a conserved system, finds equivalent regions when the parameters are tuned equally.…”

Section: Discussionmentioning

confidence: 99%

$${\text{COSNet}}_i$$: ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes

et al. 2021

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Background Upon environmental stimuli, ribosomes are surmised to undergo compositional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter ($${\text{COSNet}}_i$$ COSNet i ), a computational method to allow testing whether ribosomal proteins (rProteins) that exhibit abundance changes under specific conditions are spatially confined to particular regions within the large ribosomal complex. Results $${\text{COSNet}}_i$$ COSNet i translates experimentally determined structures into graphs, with nodes representing proteins and edges the spatial proximity between them. In its first implementation, $${\text{COSNet}}_i$$ COSNet i considers rProteins and ignores rRNA and other objects. Spatial regions are defined using a random walk with restart methodology, followed by a procedure to obtain a minimum set of regions that cover all proteins in the complex. Structural coherence is achieved by applying weights to the edges reflecting the physical proximity between purportedly contacting proteins. The weighting probabilistically guides the random-walk path trajectory. Parameter tuning during region selection provides the option to tailor the method to specific biological questions by yielding regions of different sizes with minimum overlaps. In addition, other graph community detection algorithms may be used for the $${\text{COSNet}}_i$$ COSNet i workflow, considering that they yield different sized, non-overlapping regions. All tested algorithms result in the same node kernels under equivalent regions. Based on the defined regions, available abundance change information of proteins is mapped onto the graph and subsequently tested for enrichment in any of the defined spatial regions. We applied $${\text{COSNet}}_i$$ COSNet i to the cytosolic ribosome structures of Saccharomyces cerevisiae, Oryctolagus cuniculus, and Triticum aestivum using datasets with available quantitative protein abundance change information. We found that in yeast, substoichiometric rProteins depleted from translating polysomes are significantly constrained to a ribosomal region close to the tRNA entry and exit sites. Conclusions $${\text{COSNet}}_i$$ COSNet i offers a computational method to partition multi-protein complexes into structural regions and a statistical approach to test for spatial enrichments of any given subsets of proteins. $${\text{COSNet}}_i$$ COSNet i is applicable to any multi-protein complex given appropriate structural and abundance-change data. $${\text{COSNet}}_i$$ COSNet i is publicly available as a GitHub repository https://github.com/MSeidelFed/COSNet_i and can be installed using the python installer pip.

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“…No reuse allowed without permission. The importance for protein functionality of charge configurations and clusters in their threedimensional structures has been underlined by several studies (56)(57)(58)(59). Charge permutations have been used in the NC region of the Gag protein for the Mason-Pfizer Monkey Virus (60).…”

Section: Discussionmentioning

confidence: 99%

Genetically flexible but conserved: a new essential motif in the C-ter domain of HIV-1 group M integrases

Kanja

Cappy

Lévy

et al. 2020

Preprint

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Using coevolution-network interference based on the comparison of two phylogenetically distantly related isolates, one from the main group M and the other from the minor group O of HIV-1, we identify, in the C-terminal domain (CTD) of integrase, a new functional motif constituted by four non-contiguous amino acids (N222K240N254K273). Mutating the lysines abolishes integration through decreased 3’-processing and inefficient nuclear import of reverse transcribed genomes. Solution of the crystal structures of wt and mutated CTDs shows that the motif generates a positive surface potential that is important for integration. The number of charges in the motif appears more crucial than their position within the motif. Indeed, the positions of the K could be permutated or additional K could be inserted in the motif, generally without affecting integration per se. Despite this potential genetic flexibility, the NKNK arrangement is strictly conserved in natural sequences, indicative of an effective purifying selection exerted at steps other than integration. Accordingly, reverse transcription was reduced even in the mutants that retained wt integration levels, indicating that specifically the wt sequence is optimal for carrying out the multiple functions integrase exerts. We propose that the existence of several amino acids arrangements within the motif, with comparable efficiencies of integration per se, might have constituted an asset for the acquisition of additional functions during viral evolution. IMPORTANCE Intensive studies on HIV-1 have revealed its extraordinary ability to adapt to environmental and immunological challenges, an ability that is also at the basis of antiviral treatments escape. Here, by deconvoluting the different roles of the viral integrase in the various steps of the infectious cycle, we report how the existence of alternative equally efficient structural arrangements for carrying out one function opens on the possibility of adapting to the optimisation of further functionalities exerted by the same protein. Such property provides an asset to increase the efficiency of the infectious process. On the other hand, though, the identification of this new motif provides a potential target for interfering simultaneously with multiple functions of the protein.

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On the segregation of protein ionic residues by charge type

Cited by 6 publications

References 92 publications

Spatially Enriched Paralog Rearrangements Argue Functionally Diverse Ribosomes Arise during Cold Acclimation in Arabidopsis

Spatially Enriched Paralog Rearrangements Argue Functionally Diverse Ribosomes Arise during Cold Acclimation in Arabidopsis

$${\text{COSNet}}_i$$: ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes

Genetically flexible but conserved: a new essential motif in the C-ter domain of HIV-1 group M integrases

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