A role of disordered domains in regulating protein oligomerization and stability

2014 ◽  
Vol 50 (74) ◽  
pp. 10797-10800 ◽  
Author(s):  
Ofrah Faust ◽  
Lavi Bigman ◽  
Assaf Friedler
Keyword(s):  
Thermodynamic Stability ◽  
Protein Oligomerization ◽  
Oligomeric State ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

This work describes a new role of intrinsically disordered regions in regulating the oligomeric state and thermodynamic stability of proteins.

scholarly journals Proximity labeling identifies LOTUS domain proteins that promote the formation of perinuclear germ granules in C. elegans

2021 ◽  
Author(s):  
Wen Tang ◽  
Ian F. Price ◽  
Hannah L. Hertz ◽  
Benjamin Pastore ◽  
Jillian Wagner
Keyword(s):  
Nuclear Periphery ◽  
P Granules ◽  
C Elegans ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Germ Granules ◽  
Protein Components ◽  
Labeling Method ◽  
Disordered Regions

The germline produces gametes that transmit genetic and epigenetic information to the next generation. Maintenance of germ cells and development of gametes require germ granules—well-conserved membraneless and RNA-rich organelles. The composition of germ granules is elusive owing to their dynamic nature and their exclusive expression in the germline. Using C. elegans germ granule, called P granule, as a model system, we employed a proximity-based labeling method in combination with mass spectrometry to comprehensively define its protein components. This set of experiments identified over 200 proteins, many of which contain intrinsically disordered regions. An RNAi-based screen identified factors that are essential for P granule assembly, notably EGGD-1 and EGGD-2, two previously uncharacterized LOTUS-domain proteins. Loss of eggd-1 and eggd-2 results in separation of P granules from nuclear envelope, germline atrophy and reduced fertility. We show that intrinsically disordered regions of EGGD-1 are required to anchor EGGD-1 to the nuclear periphery while its LOTUS domains are required to promote perinuclear localization of P granules. Together, our work expands the repertoire of P granule constituents and provides new insights into the role of LOTUS-domain proteins in germ granule organization.

scholarly journals Role of “dual-personality” fragments in HEV adaptation—analysis of Y-domain region

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zoya Shafat ◽  
Anwar Ahmed ◽  
Mohammad K. Parvez ◽  
Shama Parveen
Keyword(s):  
Molecular Recognition ◽  
Functional Annotation ◽  
Rna Binding ◽  
Intrinsic Disorder ◽  
Hepatitis E ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Disordered Regions

Abstract Background Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation. Results Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a “dual personality” (DP) protein due to the presence of both structured and unstructured (intrinsically disordered) regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids (Ala, Arg, Gly, Ile, Leu, Phe, Pro, Ser, Tyr, Val). Additionally, the predominance of characteristic DP residues (Thr, Arg, Gly, and Pro) further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein–protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition (PPI, RNA binding, and DNA binding) signifies the YDR’s interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities. Conclusions As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.

scholarly journals A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain–domain interactions

2017 ◽  
Vol 114 (24) ◽  
pp. 6292-6297 ◽  
Author(s):  
Carl Frieden ◽  
Hanliu Wang ◽  
Chris M. W. Ho
Keyword(s):  
Late Onset ◽  
Lipid Binding ◽  
Mass Spectrometry Data ◽  
Single Amino Acid ◽  
Protein Motions ◽  
Exchange Mass Spectrometry ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

Relative to the apolipoprotein E (apoE) E3 allele of the APOE gene, apoE4 strongly increases the risk for the development of late-onset Alzheimer’s disease. However, apoE4 differs from apoE3 by only a single amino acid at position 112, which is arginine in apoE4 and cysteine in apoE3. It remains unclear why apoE3 and apoE4 are functionally different. Described here is a proposal for understanding the functional differences between these two isoforms with respect to lipid binding. A mechanism is proposed that is based on the full-length monomeric structure of the protein, on hydrogen–deuterium exchange mass spectrometry data, and on the role of intrinsically disordered regions to control protein motions. It is proposed that lipid binds between the N-terminal and C-terminal domains and that separation of the two domains, along with the presence of intrinsically disordered regions, controls this process. The mechanism explains why apoE3 differs from apoE4 with respect to different lipid-binding specificities, why lipid increases the binding of apoE to its receptor, and why specific residues are conserved.

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