scholarly journals Low-frequency vibrational modes in G-quadruplexes reveal the mechanical properties of nucleic acids

Author(s):  
Mario González Jiménez ◽  
Gopakumar Ramakrishnan ◽  
Nikita Tukachev ◽  
Hans Martin Senn ◽  
Klaas Wynne

Low-frequency vibrations play an essential role in biomolecular processes involving DNA such as gene expression, charge transfer, drug intercalation, and DNA–protein recognition. However, understanding the vibrational basis of these mechanisms...

Author(s):  
M. González-Jiménez ◽  
G. Ramakrishnan ◽  
K. Wynne

AbstractLow-frequency vibrations play an essential role in biomolecular processes involving DNA such as gene expression, charge transfer, drug intercalation, and DNA–protein recognition. However, understanding of the vibrational basis of these mechanisms relies on theoretical models due to the lack of experimental evidence. Here we present the low-frequency vibrational spectra of G-quadruplexes (structures formed by four strands of DNA) and B-DNA characterized using femtosecond optical Kerr-effect spectroscopy. Contrary to expectation, we found that G-quadruplexes show several strongly underdamped delocalized phonon-like modes that have the potential to contribute to the biology of the DNA at the atomic level. In addition, G-quadruplexes present modes at a higher frequency than B-DNA demonstrating that changes in the stiffness of the molecule alter its gigahertz to terahertz vibrational profile. These results demonstrate that current theoretical models fail to predict basic properties of the vibrational modes of DNA.Statement of significanceA number of recent studies have identified thermally excited low-frequency vibrational modes as a key deciding factor in the biological function of DNA. However, the nature of these vibrational modes has never been established. Here, vibrational spectroscopy with unrivalled signal-to-noise in the gigahertz to terahertz range is used to determine the low-frequency Raman spectra of nucleotides and oligomeric DNAs carefully chosen to form G-quadruplexes, structures formed by four strands of DNA common in the genome. These G-quadruplexes exhibit an unusual group of highly-underdamped delocalized vibrational modes—not reproduced by any of the theoretical models in use—which are expected to be the thermally excited. This provides a new perspective on the role of low-frequency vibrational modes in protein interactions and allostery.


2020 ◽  
Vol 11 (19) ◽  
pp. 4969-4979 ◽  
Author(s):  
Yi-Tsao Chen ◽  
Haw Yang ◽  
Jhih-Wei Chu

The mechanical properties of nucleic acids underlie biological processes ranging from genome packaging to gene expression. We devise structural mechanics statistical learning method to reveal their molecular origin in terms of chemical interactions.


1994 ◽  
Vol 269 (49) ◽  
pp. 31047-31050
Author(s):  
S Jeyarajah ◽  
L M Proniewicz ◽  
H Bronder ◽  
J R Kincaid

Soft Matter ◽  
2021 ◽  
Author(s):  
Brian Tighe ◽  
Karsten Baumgarten

We determine how low frequency vibrational modes control the elastic shear modulus of Mikado networks, a minimal mechanical model for semi-flexible fiber networks. From prior work it is known that...


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
Y. P. Tsao ◽  
F. Y. Tseng ◽  
C. W. Chao ◽  
M. H. Chen ◽  
S. T. Chen

Background:Systemic lupus erythematous (SLE) is a systemic autoimmune disease with diverse etiological factors. It was recognized that interferon (IFN) signature involved in the progress of SLE. NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is a pyrin containing NLR protein that we had linked its new biological function to the cross-regulation of Toll like receptor (TLRs) and Rig-I like receptor (RIG-I) pathways. NLPR12 acts as an innate immune check-point in regulating type I IFNs expression during TLRs and RIG-I activation. The importance of NLRP12 in lupus disease activity remained to be elucidated.Objectives:To clarify the role of NLRP12 in regulating the interferon signature.Methods:Peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors for analysis of NLRP12 and IFN-α gene expression by RT-QPCR. PBMCs were applied for Chromatin immuneprecipitation (ChIP) assay and electrical mobility shift assay (EMSA) to determine the putative transcription factor that regulates NLRP12 expression. An involvement of epigenetic regulation of NLRP12 expression in SLE patients was also analyzed. Bone marrow derived dendritic cells (BMDCs) were collected from wild type mouse and Nlrp12 knocked-out mice. Another CD14+ monocytes were isolated from 10 cases of lupus patients and 8 cases of healthy control, following by stimulating different type of nucleic acids, and IFN-α and IL-6 were measured with ELISA assay. CD14+ monocytes in lupus patients were also pre-treated with IFNAR2 antibody for further nucleic acid stimulation. Two mice models were applied for evaluation the role of Nlrp12: intraperitoneal injection of TMPD (2,6,10,14-tetramethylpentadecane, or pristane) in C57BL/6 mice and Faslpr mice. Both models were conducted with and without Nlrp12 knockout.Results:NLRP12 expression was significantly lower in PBMC isolated from SLE patients compared to healthy donors. The inverse correlation was observed in NLRP12 and IFNA gene expression as well as NLRP12 expression and amount of double-stranded DNA autoantibody in SLE patients. NLRP12 expression showed negative correlations with IFN-α treatment, as well as herpes simplex virus-1 (HSV-1) infection. Results from ChIP and EMSA analysis indicated a potential transcription factor 1 (TF-1) regulating NLRP12 promoter activity. TF-1 lead to transcriptional suppression of NLRP12 in SLE PBMC, and it was gradually induced after IFN treatment. Recruitment of TF-1 to NLRP12 promoter in SLE PBMC compared to the healthy PBMC was detected, and increased when treating with IFN. Human CD14+ monocytes collected from lupus and healthy control stimulating with different type of nucleic acids revealing significant increasing level of IFN-α and IL-6 in lupus patients. Among animal models, both pristine induced mice and Faslpr mice revealed increasing autoantibodies production and severity of glomerulonephritis in Nlrp12-/- group in comparison with Nlrp12+/+ ones, indicating the role of NLRP12 in maintaining positive interferon signature as well as disease activity.Conclusion:Expression level of NLRP1.2 has been demonstrated to be a biomarker of disease activity in SLE patients. The NLRP12 was involved in the interferon signature, which was also negatively regulated by TF-1. Both clinical samples and animal models revealed NLRP12 in maintaining the positive interferon signature, indicating the possible role of exacerbating factor for lupus disease activity.Disclosure of Interests:None declared


2014 ◽  
Vol 118 (30) ◽  
pp. 9037-9045 ◽  
Author(s):  
Xing Yin ◽  
Jing Kong ◽  
Arnie De Leon ◽  
Yongle Li ◽  
Zhijie Ma ◽  
...  

2015 ◽  
Vol 48 (12) ◽  
pp. 3306-3311 ◽  
Author(s):  
Gail M. Thornton ◽  
Devin B. Lemmex ◽  
Yohei Ono ◽  
Cara J. Beach ◽  
Carol R. Reno ◽  
...  

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