scholarly journals Signalling assemblies: the odds of symmetry

2017 ◽  
Vol 45 (3) ◽  
pp. 599-611 ◽  
Author(s):  
Gábor Maksay ◽  
Joseph A. Marsh
Keyword(s):  
Transcription Factors ◽  
Structure Determination ◽  
Protein Complex ◽  
Protein Complexes ◽  
Asymmetric Structures ◽  
Traditional Structure ◽  
Dominant Feature ◽  
Transmembrane Channels ◽  
Determination Methods

The assembly of proteins into complexes is fundamental to nearly all biological signalling processes. Symmetry is a dominant feature of the structures of experimentally determined protein complexes, observed in the vast majority of homomers and many heteromers. However, some asymmetric structures exist, and asymmetry also often forms transiently, intractable to traditional structure determination methods. Here, we explore the role of protein complex symmetry and asymmetry in cellular signalling, focusing on receptors, transcription factors and transmembrane channels, among other signalling assemblies. We highlight a recurrent tendency for asymmetry to be crucial for signalling function, often being associated with activated states. We conclude with a discussion of how consideration of protein complex symmetry and asymmetry has significant potential implications and applications for pharmacology and human disease.

scholarly journals MiR193a Modulation and Podocyte Phenotype

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1004
Author(s):  
Alok Jha ◽  
Shourav Saha ◽  
Kamesh Ayasolla ◽  
Himanshu Vashistha ◽  
Ashwani Malhotra ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Markers ◽  
Promoter Region ◽  
Therapeutic Strategy ◽  
Protein Complexes ◽  
Md Simulations ◽  
Tertiary Structures ◽  
Docking Approach ◽  
Apolipoprotein L1

Apolipoprotein L1 (APOL1)-miR193a axis has been reported to play a role in the maintenance of podocyte homeostasis. In the present study, we analyzed transcription factors relevant to miR193a in human podocytes and their effects on podocytes’ molecular phenotype. The motif scan of the miR193a gene provided information about transcription factors, including YY1, WT1, Sox2, and VDR-RXR heterodimer, which could potentially bind to the miR193a promoter region to regulate miR193a expression. All structure models of these transcription factors and the tertiary structures of the miR193a promoter region were generated and refined using computational tools. The DNA-protein complexes of the miR193a promoter region and transcription factors were created using a docking approach. To determine the modulatory role of miR193a on APOL1 mRNA, the structural components of APOL1 3’ UTR and miR193a-5p were studied. Molecular Dynamic (MD) simulations validated interactions between miR193a and YY1/WT1/Sox2/VDR/APOL1 3′ UTR region. Undifferentiated podocytes (UPDs) displayed enhanced miR193a, YY1, and Sox2 but attenuated WT1, VDR, and APOL1 expressions, whereas differentiated podocytes (DPDs) exhibited attenuated miR193a, YY1, and Sox2 but increased WT1, VDR, APOL1 expressions. Inhibition of miR193a in UPDs enhanced the expression of APOL1 as well as of podocyte molecular markers; on the other hand, DPD-transfected with miR193a plasmid showed downing of APOL1 as well as podocyte molecular markers suggesting a causal relationship between miR193a and podocyte molecular markers. Silencing of YY1 and Sox2 in UPDs decreased the expression of miR193a but increased the expression of VDR, and CD2AP (a marker of DPDs); in contrast, silencing of WT1 and VDR in DPDs enhanced the expression of miR193a, YY1, and Sox2. Since miR193a-downing by Vitamin D receptor (VDR) agonist not only enhanced the mRNA expression of APOL1 but also of podocyte differentiating markers, suggest that down-regulation of miR193a could be used to enhance the expression of podocyte differentiating markers as a therapeutic strategy.

scholarly journals SWATH-MS co-expression profiles reveal paralogue interference in protein complex evolution

2020 ◽  
Author(s):  
Luzia Stalder ◽  
Amir Banaei-Esfahani ◽  
Rodolfo Ciuffa ◽  
Joshua L Payne ◽  
Ruedi Aebersold
Keyword(s):  
Protein Complex ◽  
Large Scale ◽  
Protein Complexes ◽  
Expression Profiles ◽  
Functional Divergence ◽  
Expression Patterns ◽  
Potential Mechanism ◽  
Evolutionary Trajectories ◽  
Pattern Distribution

AbstractUnderstanding the conservation and evolution of protein complexes is of critical value to decode their function in physiological and pathological processes. One prominent proposal posits gene duplication as a potential mechanism for protein complex evolution. In this study we take advantage of large-scale proteome expression datasets to systematically investigate the role of paralogues, and specifically self-interacting paralogues, in shaping the evolutionary trajectories of protein complexes. First, we show that protein co-expression derived from quantitative proteomic matrices is a good indicator for complex membership and is conserved across species. Second, we suggest that paralogues are commonly strongly co-expressed and that for the subset of paralogues that show diverging co-expression patterns, the divergent co-expression patterns reflect both sequence and functional divergence. Finally, on this basis, we show that homomeric paralogues known to be part of protein complexes display a unique co-expression pattern distribution, with a subset of them being highly diverging. These findings support the idea that homomeric paralogues can avoid cross-interference by diversifying their expression patterns, and corroborates the role of this mechanism as a force shaping protein complex evolution and specialization.

Structure Determination of Protein−Protein Complexes Using NMR Chemical Shifts: Case of an Endonuclease Colicin−Immunity Protein Complex

2008 ◽  
Vol 130 (47) ◽  
pp. 15990-15996 ◽  
Author(s):  
Rinaldo W. Montalvao ◽  
Andrea Cavalli ◽  
Xavier Salvatella ◽  
Tom L. Blundell ◽  
Michele Vendruscolo
Keyword(s):  
Structure Determination ◽  
Protein Complex ◽  
Protein Complexes ◽  
Chemical Shifts ◽  
Immunity Protein ◽  
Nmr Chemical Shifts

scholarly journals Beyond the Black Box: Interactive Global Docking of Protein Complexes

2008 ◽  
Vol 16 (4) ◽  
pp. 6-9 ◽  
Author(s):  
Jochen Heyd ◽  
Stefan Birmanns
Keyword(s):  
Protein Complexes ◽  
Natural State ◽  
Large Protein ◽  
X Ray Crystallography ◽  
The Past ◽  
Cryo Electron Microscopy ◽  
Traditional Structure ◽  
Determination Methods ◽  
Microscopy Techniques ◽  
Structure Of Proteins

A key to understanding the function of biological systems is the visualization of their natural state, ideally in a natural environment. At a molecular level, this is challenging. Traditional experimental techniques, like X-ray crystallography, can provide the atomic structure of proteins, but only by removing them from their native surroundings and forcing them into crystals. Over the past decade, microscopy techniques have emerged as alternatives to these traditional structure determination methods, with the advantage of visualizing molecules in a near-native state. Given the current focus of structural biology on interactions between proteins and better understanding of large protein complexes, cryo-electron microscopy (cryo-EM) has become a valuable tool.

The role of Forkhead Box O 3a (FoxO3a) Transcription Factors in the Pathogenesis of Pulmonary Fibrosis

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
HM Al-Tamari ◽  
M Eschenhagen ◽  
A Schmall ◽  
R Savai ◽  
HA Ghofrani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pulmonary Fibrosis ◽  
Forkhead Box
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