G-Quadruplex Secondary Structure Obtained from Circular Dichroism Spectroscopy

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2017 Oct 28

PMID 29076232

Citations 175

Authors

Rafael Del Villar-Guerra

John O Trent

Jonathan B Chaires

Affiliations

Soon will be listed here.

Abstract

A curated library of circular dichroism spectra of 23 G-quadruplexes of known structure was built and analyzed. The goal of this study was to use this reference library to develop an algorithm to derive quantitative estimates of the secondary structure content of quadruplexes from their experimental CD spectra. Principal component analysis and singular value decomposition were used to characterize the reference spectral library. CD spectra were successfully fit to obtain estimates of the amounts of base steps in anti-anti, syn-anti or anti-syn conformations, in diagonal or lateral loops, or in other conformations. The results show that CD spectra of nucleic acids can be analyzed to obtain quantitative structural information about secondary structure content in an analogous way to methods used to analyze protein CD spectra.

Citing Articles

Protocol for circular dichroism spectral analysis of the thermal stability of CpG-methylated quadruplex structures.

Moriya M, Oyama T, Goto M, Ikebukuro K, Yoshida W STAR Protoc. 2025; 6(1):103646.

PMID: 39985771 PMC: 11904582. DOI: 10.1016/j.xpro.2025.103646.

Alternative Approach to Sequence-Specific Recognition of DNA: Cooperative Stacking of Dication Dimers─Sensitivity to Compound Curvature, Aromatic Structure, and DNA Sequence.

Paul A, Terrell J, Farahat A, Ogbonna E, Kumar A, Boykin D ACS Chem Biol. 2025; 20(2):489-506.

PMID: 39920086 PMC: 11851451. DOI: 10.1021/acschembio.4c00800.

Quencher-Free Fluorescence Monitoring of G-Quadruplex Folding.

Parada Z, Hoog T, Adamala K, Engelhart A ACS Omega. 2025; 10(3):3176-3181.

PMID: 39895733 PMC: 11780409. DOI: 10.1021/acsomega.4c10720.

Early events in G-quadruplex folding captured by time-resolved small-angle X-ray scattering.

Monsen R, Sabo T, Gray R, Hopkins J, Chaires J Nucleic Acids Res. 2025; 53(3).

PMID: 39883009 PMC: 11780883. DOI: 10.1093/nar/gkaf043.

A Label-Free Colorimetric Aptasensor for Flavokavain B Detection.

Ke S, Wang N, Chen X, Tian J, Li J, Yu B Sensors (Basel). 2025; 25(2).

PMID: 39860936 PMC: 11768667. DOI: 10.3390/s25020569.

References

Sreerama N, Venyaminov S, Woody R . Estimation of the number of alpha-helical and beta-strand segments in proteins using circular dichroism spectroscopy. Protein Sci. 1999; 8(2):370-80. PMC: 2144265. DOI: 10.1110/ps.8.2.370. View

Clarke Miller M, Trent J . Resolution of quadruplex polymorphism by size-exclusion chromatography. Curr Protoc Nucleic Acid Chem. 2011; Chapter 17:Unit17.3. PMC: 3963359. DOI: 10.1002/0471142700.nc1703s45. View

Vorlickova M, Kejnovska I, Bednarova K, Renciuk D, Kypr J . Circular dichroism spectroscopy of DNA: from duplexes to quadruplexes. Chirality. 2012; 24(9):691-8. DOI: 10.1002/chir.22064. View

Chaires J, Dean W, Le H, Trent J . Hydrodynamic Models of G-Quadruplex Structures. Methods Enzymol. 2015; 562:287-304. PMC: 5705227. DOI: 10.1016/bs.mie.2015.04.011. View

Garbett N, Mekmaysy C, Chaires J . Sedimentation velocity ultracentrifugation analysis for hydrodynamic characterization of G-quadruplex structures. Methods Mol Biol. 2009; 608:97-120. PMC: 3008627. DOI: 10.1007/978-1-59745-363-9_7. View

Greenfield N . Using circular dichroism spectra to estimate protein secondary structure. Nat Protoc. 2007; 1(6):2876-90. PMC: 2728378. DOI: 10.1038/nprot.2006.202. View

Hennessey Jr J, Johnson Jr W . Information content in the circular dichroism of proteins. Biochemistry. 1981; 20(5):1085-94. DOI: 10.1021/bi00508a007. View

Lees J, Miles A, Wien F, Wallace B . A reference database for circular dichroism spectroscopy covering fold and secondary structure space. Bioinformatics. 2006; 22(16):1955-62. DOI: 10.1093/bioinformatics/btl327. View

Compton L, Johnson Jr W . Analysis of protein circular dichroism spectra for secondary structure using a simple matrix multiplication. Anal Biochem. 1986; 155(1):155-67. DOI: 10.1016/0003-2697(86)90241-1. View

10.

Webba Da Silva M . Geometric formalism for DNA quadruplex folding. Chemistry. 2007; 13(35):9738-45. DOI: 10.1002/chem.200701255. View

11.

Randazzo A, Spada G, Webba Da Silva M . Circular dichroism of quadruplex structures. Top Curr Chem. 2012; 330:67-86. DOI: 10.1007/128_2012_331. View

12.

Cantor C, WARSHAW M, Shapiro H . Oligonucleotide interactions. 3. Circular dichroism studies of the conformation of deoxyoligonucleotides. Biopolymers. 1970; 9(9):1059-77. DOI: 10.1002/bip.1970.360090909. View

13.

Masiero S, Trotta R, Pieraccini S, De Tito S, Perone R, Randazzo A . A non-empirical chromophoric interpretation of CD spectra of DNA G-quadruplex structures. Org Biomol Chem. 2010; 8(12):2683-92. DOI: 10.1039/c003428b. View

14.

Gray D, Wen J, Gray C, Repges R, Repges C, Raabe G . Measured and calculated CD spectra of G-quartets stacked with the same or opposite polarities. Chirality. 2007; 20(3-4):431-40. DOI: 10.1002/chir.20455. View

15.

Johnson W . Analyzing protein circular dichroism spectra for accurate secondary structures. Proteins. 1999; 35(3):307-12. View

16.

Hansel-Hertsch R, Di Antonio M, Balasubramanian S . DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential. Nat Rev Mol Cell Biol. 2017; 18(5):279-284. DOI: 10.1038/nrm.2017.3. View

17.

Compton L, Mathews C, Johnson Jr W . The conformation of T4 bacteriophage dihydrofolate reductase from circular dichroism. J Biol Chem. 1987; 262(27):13039-43. View

18.

Jaumot J, Eritja R, Navea S, Gargallo R . Classification of nucleic acids structures by means of the chemometric analysis of circular dichroism spectra. Anal Chim Acta. 2009; 642(1-2):117-26. DOI: 10.1016/j.aca.2008.12.052. View

19.

Sreerama N, Woody R . Computation and analysis of protein circular dichroism spectra. Methods Enzymol. 2004; 383:318-51. DOI: 10.1016/S0076-6879(04)83013-1. View

20.

Villar-Guerra R, Gray R, Chaires J . Characterization of Quadruplex DNA Structure by Circular Dichroism. Curr Protoc Nucleic Acid Chem. 2017; 68:17.8.1-17.8.16. PMC: 5334661. DOI: 10.1002/cpnc.23. View