Structure and function analysis of protein–nucleic acid complexes

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.

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ChemInform Abstract: Applications of Psoralens as Probes of Nucleic Acid Structure and Function

ChemInform ◽

10.1002/chin.199116327 ◽

2010 ◽

Vol 22 (16) ◽

pp. no-no

Author(s):

Y. B. SHI ◽

S. E. LIPSON ◽

D. Y. CHI ◽

H. P. SPIELMANN ◽

J. A. MONFORTE ◽

...

Keyword(s):

Nucleic Acid ◽

Structure And Function ◽

Nucleic Acid Structure ◽

And Function ◽

Acid Structure

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Abstract 112: Cardiac-specific Constitutive Activation of Nrf2 Induces Reductive Stress and Pathological Cardiac Remodeling

Circulation Research ◽

10.1161/res.121.suppl_1.112 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Gobinath Shanmugam ◽

Madhusudhanan Narasimhan ◽

Jolyn Fernandes ◽

Kevin Whitehead ◽

Silvio H Litovsky ◽

...

Keyword(s):

Cardiac Remodeling ◽

Function Analysis ◽

Radical Scavenging ◽

Structure And Function ◽

Heart Weight ◽

Wall Thickening ◽

Antioxidant Genes ◽

Reductive Stress ◽

Chronic Activation ◽

And Function

Background: Heart failure is a growing cause of human morbidity and mortality. Supplementations of free radical scavenging antioxidants have largely failed to protect the myocardium from oxidative stress diseases. While endogenous transcriptional activation of antioxidants appears to be promising, their chronic effects are unknown. Here, we tested a hypothesis that chronic activation of antioxidant system will result in reductive stress (RS) and lead to pathological cardiac hypertrophy. Methods: Novel transgenic (TG) mice expressing constitutively active Nrf2 in the heart (α-MHC-caNrf2-TG) and their littermates were used to study the effects on structure and function of the myocardium. Myocardial glutathione redox state (GSH/GSSG), transcript levels (qPCR), and protein (immunoblotting) for Nrf2-related antioxidants and structure and function analysis (echocardiography - Vevo2100 Imager) in Non-transgenic (NTg), TG-low and TG-high mice (n=6-12/gp.) were performed at 6-8 months of age. Further, changes in cardiomyocytes and rate of survival in TG mice were analyzed. Results: Kaplan-Meier survival plots demonstrated 10 and 40% mortality in TG-low and TG-high, respectively, compared to NTG by 60 weeks of age. The myocardial glutathione and its redox ratio (GSH/GSSG) were significantly increased (p<0.05) in the TG-low and TG-high compared with NTg mice indicates development of RS. A significant increase in Nrf2-ARE (promoter) binding with increased expression of antioxidant genes and proteins (p<0.05) were noted in TG vs. NTg mice. Increased heart-to-body weight and heart weight to tibia length ratios were prominent in TG-high relative to NTg or TG-low mice. Histological analyses (WGA, H&E staining) showed increased cardiomyocyte size, ventricular wall thickening and decreased chamber volume in TG mice. Echocardiography analyses revealed significant hypertrophic cardiomyopathy with abnormally increased ejection fraction (HCM i EF) due to chronic reductive stress. Conclusion: Thus, basal attenuation of the obligatory oxidative signaling with chronic activation of Nrf2-antioxidants could shift the redox equilibrium to “reductive” side and thereby causing pathological cardiac remodeling.

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Synthetic Biology Open Language Visual (SBOL Visual) Version 2.1

Journal of Integrative Bioinformatics ◽

10.1515/jib-2018-0101 ◽

2019 ◽

Vol 16 (2) ◽

Cited By ~ 6

Author(s):

Curtis Madsen ◽

Angel Goni Moreno ◽

Zachary Palchick ◽

Umesh P ◽

Nicholas Roehner ◽

...

Keyword(s):

Nucleic Acid ◽

Synthetic Biology ◽

Molecular Species ◽

Chemical Process ◽

Structure And Function ◽

Genomic Context ◽

Functional Relationships ◽

Synthetic Biology Open Language ◽

And Function ◽

Biological Organisms

AbstractPeople who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species . Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.1 of SBOL Visual, which builds on the prior SBOL Visual 2.0 standard by expanding diagram syntax to include methods for showing modular structure and mappings between elements of a system, interactions arrows that can split or join (with the glyph at the split or join indicating either superposition or a chemical process), and adding new glyphs for indicating genomic context (e.g., integration into a plasmid or genome) and for stop codons.

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Structure and Function of Multimeric G-Quadruplexes

Molecules ◽

10.3390/molecules24173074 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3074 ◽

Cited By ~ 25

Author(s):

Sofia Kolesnikova ◽

Edward A. Curtis

Keyword(s):

Nucleic Acid ◽

Building Blocks ◽

Structure And Function ◽

Limited Information ◽

Functional Elements ◽

Future Studies ◽

And Function ◽

Nucleic Acid Structures ◽

Sequence Requirements ◽

Order Structures

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers, but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review, we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

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