Exploring the dark foldable proteome by considering hydrophobic amino acids topology

Bitard‐Feildel, Tristan; Callebaut, Isabelle

doi:10.1038/srep41425

Cited by 24 publications

(38 citation statements)

References 64 publications

(113 reference statements)

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“…The focus of this study however, was the Homo Sapiens and other model organisms where it can be concluded that the amount of dark proteome present in them is still high, whereas in higher eukaryotes like mouse and human, it is around 50%. The results presented above are consistent with previous works (6,23), since Arabidopsis dark proteins are mainly located in extracellular space, cellular membrane and endoplasmic reticulum membranes. C. Elegans dark proteins are present again in cell membrane where they are secreted.…”

Section: Discussionsupporting

confidence: 93%

Dark Proteome Database: Studies on Dark Proteins

Perdigão¹

2019

Preprint

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The dark proteome as we define it, is the part of the proteome where 3D structure has not been observed either by homology modeling or by experimental characterization in the protein universe. From the 550.116 proteins available in Swiss-Prot (as of July 2016) 43.2% of the Eukarya universe and 49.2% of the Virus universe are part of the dark proteome. In Bacteria and Archaea, the percentage of the dark proteome presence is significantly less, with 12.6% and 13.3% respectively. In this work, we present the map of the dark proteome in Human and in other model organisms. The most significant result is that around 40%-50% of the proteome of these organisms are still in the dark, where the higher percentages belong to higher eukaryotes (mouse and human organisms). Due to the amount of darkness present in the human organism being more than 50%, deeper studies were made, including the identification of 'dark' genes that are responsible for the production of the so-called dark proteins, as well as, the identification of the 'dark' organs where dark proteins are over represented, namely heart, cervical mucosa and natural killer cells. This is a step forward in the direction of the human dark proteome.

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Section: Discussionsupporting

confidence: 93%

Dark Proteome Database: Studies on Dark Proteins

Perdigão¹

2019

Preprint

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“…It can be observed that novel orphHCA domains show an overall higher fraction of disorder than novel Pfam domains, which is in agreement with a recent study showing that unannotated protein domains have a high disorder content [75]. 'New' domains that can be found in Pfam MDA (i.e.…”

Section: Structural Propertiessupporting

confidence: 90%

Origins and structural properties of novel andde novoprotein domains during insect evolution

et al. 2018

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Over long time scales, protein evolution is characterized by modular rearrangements of protein domains. Such rearrangements are mainly caused by gene duplication, fusion and terminal losses. To better understand domain emergence mechanisms we investigated 32 insect genomes covering a speciation gradient ranging from ~ 2 to ~ 390 mya. We use established domain models and foldable domains delineated by hydrophobic cluster analysis (HCA), which does not require homologous sequences, to also identify domains which have likely arisen de novo, that is, from previously noncoding DNA. Our results indicate that most novel domains emerge terminally as they originate from ORF extensions while fewer arise in middle arrangements, resulting from exonization of intronic or intergenic regions. Many novel domains rapidly migrate between terminal or middle positions and single- and multidomain arrangements. Young domains, such as most HCA-defined domains, are under strong selection pressure as they show signals of purifying selection. De novo domains, linked to ancient domains or defined by HCA, have higher degrees of intrinsic disorder and disorder-to-order transition upon binding than ancient domains. However, the corresponding DNA sequences of the novel domains of de novo origins could only rarely be found in sister genomes. We conclude that novel domains are often recruited by other proteins and undergo important structural modifications shortly after their emergence, but evolve too fast to be characterized by cross-species comparisons alone.

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“…By contrast, regions lacking HCs or possessing only small and/or scarcely distributed HCs generally correspond to fully disordered sequences and/or flexible linkers. These features that can be deduced from HCA have been supported in a quantitative way by developing a tool, called SEG‐HCA, allowing to automatically delineate regions with high density in HCs (foldable regions) . The relevance of such approach has been supported by considering the coverage of domain and structure databases by the SEG‐HCA predictions .…”

Section: Hca and The Delineation Of Foldable Regionsmentioning

confidence: 99%

Order in Disorder as Observed by the “Hydrophobic Cluster Analysis” of Protein Sequences

et al. 2018

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Hydrophobic cluster analysis (HCA) is an original approach for protein sequence analysis, which provides access to the foldable repertoire of the protein universe, including yet unannotated protein segments ("dark proteome"). Foldable segments correspond to ordered regions, as well as to intrinsically disordered regions (IDRs) undergoing disorder to order transitions. In this review, how HCA can be used to give insight into this last category of foldable segments is illustrated, with examples matching known 3D structures. After reviewing the HCA principles, examples of short foldable segments are given, which often contain short linear motifs, typically matching hydrophobic clusters. These segments become ordered upon contact with partners, with secondary structure preferences generally corresponding to those observed in the 3D structures within the complexes. Such small foldable segments are sometimes larger than the segments of known 3D structures, including flanking hydrophobic clusters that may be critical for interaction specificity or regulation, as well as intervening sequences allowing fuzziness. Cases of larger conditionally disordered domains are also presented, with lower density in hydrophobic clusters than well-folded globular domains or with exposed hydrophobic patches, which are stabilized by interaction with partners.

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Exploring the dark foldable proteome by considering hydrophobic amino acids topology

Cited by 24 publications

References 64 publications

Dark Proteome Database: Studies on Dark Proteins

Dark Proteome Database: Studies on Dark Proteins

Origins and structural properties of novel andde novoprotein domains during insect evolution

Order in Disorder as Observed by the “Hydrophobic Cluster Analysis” of Protein Sequences

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