scholarly journals Variable absorption of mutational trends by prion-forming domains during Saccharomycetes evolution

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9669
Author(s):  
Paul M. Harrison
Keyword(s):  
Large Population ◽  
Selective Constraint ◽  
Alternative States ◽  
Functional Protein ◽  
Selection Pressures ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Intrinsic Protein Disorder ◽  
Lysine Residues

Prions are self-propagating alternative states of protein domains. They are linked to both diseases and functional protein roles in eukaryotes. Prion-forming domains in Saccharomyces cerevisiae are typically domains with high intrinsic protein disorder (i.e., that remain unfolded in the cell during at least some part of their functioning), that are converted to self-replicating amyloid forms. S. cerevisiae is a member of the fungal class Saccharomycetes, during the evolution of which a large population of prion-like domains has appeared. It is still unclear what principles might govern the molecular evolution of prion-forming domains, and intrinsically disordered domains generally. Here, it is discovered that in a set of such prion-forming domains some evolve in the fungal class Saccharomycetes in such a way as to absorb general mutation biases across millions of years, whereas others do not, indicating a spectrum of selection pressures on composition and sequence. Thus, if the bias-absorbing prion formers are conserving a prion-forming capability, then this capability is not interfered with by the absorption of bias changes over the duration of evolutionary epochs. Evidence is discovered for selective constraint against the occurrence of lysine residues (which likely disrupt prion formation) in S. cerevisiae prion-forming domains as they evolve across Saccharomycetes. These results provide a case study of the absorption of mutational trends by compositionally biased domains, and suggest methodology for assessing selection pressures on the composition of intrinsically disordered regions.

scholarly journals Structural propensity database of proteins

2017 ◽  
Author(s):  
Kamil Tamiola ◽  
Matthew M Heberling ◽  
Jan Domanski
Keyword(s):  
Structural Dynamics ◽  
Protein Function ◽  
Chemical Shifts ◽  
Protein Disorder ◽  
Computational Biophysics ◽  
Intrinsic Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Intrinsic Protein Disorder ◽  
Structural Insights

AbstractAn overwhelming amount of experimental evidence suggests that elucidations of protein function, interactions, and pathology are incomplete without inclusion of intrinsic protein disorder and structural dynamics. Thus, to expand our understanding of intrinsic protein disorder, we have created a database of secondary structure (SS) propensities for proteins (dSPP) as a reference resource for experimental research and computational biophysics. The dSPP comprises SS propensities of 7,094 unrelated proteins, as gauged from NMR chemical shift measurements in solution and solid state. Here, we explain the concept of SS propensity and analyze dSPP entries of therapeutic relevance, α-synuclein, MOAG-4, and the ZIKA NS2B-NS3 complex to show: (1) how propensity mapping generates novel structural insights into intrinsically disordered regions of pathologically relevant proteins, (2) how computational biophysics tools can benefit from propensity mapping, and (3) how the residual disorder estimation based on NMR chemical shifts compares with sequence-based disorder predictors. This work demonstrates the benefit of propensity estimation as a method that reports both on protein structure, lability, and disorder.

scholarly journals Computational Characterization of the mtORF of Pocilloporid Corals: Insights into Protein Structure and Function in Stylophora Lineages from Contrasting Environments

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 324
Author(s):  
Banguera-Hinestroza ◽  
Ferrada ◽  
Sawall ◽  
Flot
Keyword(s):  
Red Sea ◽  
Metal Binding ◽  
Tandem Repeats ◽  
Environmental Changes ◽  
Transmembrane Protein ◽  
Domain Architecture ◽  
Thermal Adaptation ◽  
Functional Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

More than a decade ago, a new mitochondrial Open Reading Frame (mtORF) was discovered in corals of the family Pocilloporidae and has been used since then as an effective barcode for these corals. Recently, mtORF sequencing revealed the existence of two differentiated Stylophora lineages occurring in sympatry along the environmental gradient of the Red Sea (18.5°C to 33.9°C). In the endemic Red Sea lineage RS_LinB, the mtORF and the heat shock protein gene hsp70 uncovered similar phylogeographic patterns strongly correlated with environmental variations. This suggests that the mtORF too might be involved in thermal adaptation. Here, we used computational analyses to explore the features and putative function of this mtORF. In particular, we tested the likelihood that this gene encodes a functional protein and whether it may play a role in adaptation. Analyses of full mitogenomes showed that the mtORF originated in the common ancestor of Madracis and other pocilloporids, and that it encodes a transmembrane protein differing in length and domain architecture among genera. Homology-based annotation and the relative conservation of metal-binding sites revealed traces of an ancient hydrolase catalytic activity. Furthermore, signals of pervasive purifying selection, lack of stop codons in 1830 sequences analyzed, and a codon-usage bias similar to that of other mitochondrial genes indicate that the protein is functional, i.e., not a pseudogene. Other features, such as intrinsically disordered regions, tandem repeats, and signals of positive selection particularly in Stylophora RS_LinB populations, are consistent with a role of the mtORF in adaptive responses to environmental changes.

scholarly journals Ubiquitin and Not Only Unfolded Domains Drives Toscana Virus Non-Structural NSs Protein Degradation

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1153
Author(s):  
Gianni Gori Savellini ◽  
Luca Bini ◽  
Assunta Gagliardi ◽  
Gabriele Anichini ◽  
Claudia Gandolfo ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Cellular Level ◽  
Structural Protein ◽  
Toscana Virus ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Inhibitory Function ◽  
Ubiquitin System ◽  
Lysine Residues ◽  
The Stability

The non-structural protein NSs of the Phenuiviridae family members appears to have a role in the host immunity escape. The stability of Toscana virus (TOSV) NSs protein was tested by a cycloheximide (CHX) chase approach on cells transfected with NSs deleted versions fused to a reporter gene. The presence of intrinsically disordered regions (IDRs) both at the C- and N-terminus appeared to affect the protein stability. Indeed, the NSsΔC and NSsΔN proteins were more stable than the wild-type NSs counterpart. Since TOSV NSs exerts its inhibitory function by triggering RIG-I for proteasomal degradation, the interaction of the ubiquitin system and TOSV NSs was further examined. Chase experiments with CHX and the proteasome inhibitor MG-132 demonstrated the involvement of the ubiquitin-proteasome system in controlling NSs protein amount expressed in the cells. The analysis of TOSV NSs by mass spectrometry allowed the direct identification of K104, K109, K154, K180, K244, K294, and K298 residues targeted for ubiquitination. Analysis of NSs K-mutants confirmed the presence and the important role of lysine residues located in the central and the C-terminal parts of the protein in controlling the NSs cellular level. Therefore, we directly demonstrated a new cellular pathway involved in controlling TOSV NSs fate and activity, and this opens the way to new investigations among more pathogenic viruses of the Phenuiviridae family.

scholarly journals New classification of intrinsic disorder in the Human proteome

2018 ◽  
Author(s):  
Antonio Deiana ◽  
Sergio Forcelloni ◽  
Alessandro Porrello ◽  
Andrea Giansanti
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Chemical Properties ◽  
Intrinsic Disorder ◽  
Disordered Proteins ◽  
General Category ◽  
Nucleic Acid Binding ◽  
Functional Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

ABSTRACTWe propose a new, sequence-only, classification of intrinsically disordered human proteins which is based on two parameters: dr, the percentage of disordered residues, and Ld, the length of the longest disordered segment in the sequence. Depending on dr and Ld, we distinguish five variants: i) ordered proteins (ORDs); ii) not disordered proteins (NDPsj; (iii) proteins with intrinsically disordered regions (PDRs); iv) intrinsically disordered proteins (IDPs) and v) proteins with fragmented disorder (FRAGs). PDRs have been considered in the general category of intrinsically disordered proteins for a long time. We show that PDRs are closer to globular, ordered proteins (ORDs and NDPs) than to disordered ones (IDPs), both in amino acid composition and functionally. Moreover, NDPs and PDRs are uniformly spread over several functional protein classes, whereas IDPs are concentrated only on two, namely nucleic acid binding proteins and transcription factors, which are just a subset of the functions that are commonly associated with protein intrinsic disorder. As a conclusion, PDRs and IDPs should be considered, in future classifications, as distinct variants of disordered proteins, with different physical-chemical properties and functional spectra.

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