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SPECIAL ISSUE: Recent Advances in Biomolecular Modeling and Simulation; Guest editors: Guohui Li and John ZhangNo Access

SPECIFIC BINDING OF A SHORT miRNA SEQUENCE BY ZINC KNUCKLES OF Lin28: A MOLECULAR DYNAMICS SIMULATION STUDY

National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing, 210093, P. R. China

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National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing, 210093, P. R. China

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National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing, 210093, P. R. China

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https://doi.org/10.1142/S0219633613410150Cited by:0 (Source: Crossref)

Abstract

Protein Lin28 recognizes pre-let-7 microRNAs (miRNAs) through direct interactions between its zinc-knuckle type zinc-finger (ZnF) domains and the terminal loop of pre-let-7, resulting in the inhibition of the synthesis of mature let-7 miRNAs. Despite the physiological importance, the involved conformational changes and energetic factors contributing to the binding affinity and specificity remain unclear. We conducted molecular dynamics (MD) simulations in conjunction with molecular mechanics/generalized born surface area (MM/GBSA) and energy decomposition calculations to investigate the RNA binding-induced conformational changes of the ZnFs and the residual level energetic factors that influence the binding affinity and specificity. We showed that the binding of the RNA results in the inter-domain conformational changes of the two ZnF domains, including changes of the spatial relationships of several nucleobase-binding amino acids. We also observed mutation-induced weakening of the affinity of the Lin28–pre-let-7 binding, which reveals the importance of the stacking interactions between the side-chains of Tyr140, His148, His162 and the bases of nucleic acid G2 and G5 in the specific recognition of pre-let-7 by the ZnFs of Lin28.

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References

N. Bushati and S. M. Cohen, Annu. Rev. Cell Dev. Biol. 23, 175 (2007), DOI: 10.1146/annurev.cellbio.23.090506.123406. Crossref, Web of Science, Google Scholar
D. P. Bartel, Cell 136, 215 (2009), DOI: 10.1016/j.cell.2009.01.002. Crossref, Web of Science, Google Scholar
J. Krol, I. Loedige and W. Filipowicz, Nat. Rev. Genet. 11, 597 (2010). Crossref, Web of Science, Google Scholar
S. R. Viswanathan, G. Q. Daley and R. I. Gregory, Science 320, 97 (2008), DOI: 10.1126/science.1154040. Crossref, Web of Science, Google Scholar
S. R. Viswanathan and G. Q. Daley, Cell 140, 445 (2010), DOI: 10.1016/j.cell.2010.02.007. Crossref, Web of Science, Google Scholar
I. Büssing, F. J. Slack and H. Grosshans, Trends. Mol. Med. 14, 400 (2008). Crossref, Web of Science, Google Scholar
F. Yuet al., Cell 131, 1109 (2007), DOI: 10.1016/j.cell.2007.10.054. Crossref, Web of Science, Google Scholar
M. A. Newman, J. M. Thomson and S. M. Hammond, RNA 14, 1539 (2008), DOI: 10.1261/rna.1155108. Crossref, Web of Science, Google Scholar
I. Heoet al., Mol. Cell 32, 276 (2008), DOI: 10.1016/j.molcel.2008.09.014. Crossref, Web of Science, Google Scholar
A. Rybaket al., Nature. Cell Biol. 10, 987 (2008), DOI: 10.1038/ncb1759. Crossref, Web of Science, Google Scholar
N. J. Lehrbachet al., Nature. Struct. Biol. 16, 1016 (2009), DOI: 10.1038/nsmb.1675. Crossref, Google Scholar
J. P. Hagan, E. Piskounova and R. I. Gregory, Nature. Struct. Biol. 16, 1021 (2009), DOI: 10.1038/nsmb.1676. Crossref, Google Scholar
I. Heoet al., Cell 138, 696 (2009), DOI: 10.1016/j.cell.2009.08.002. Crossref, Web of Science, Google Scholar
B. Xu and Y. Huang, Nucleic. Acids. Res. 37, 4256 (2009), DOI: 10.1093/nar/gkp372. Crossref, Web of Science, Google Scholar
C. Qiuet al., Nucleic. Acids. Res. 38, 1240 (2010), DOI: 10.1093/nar/gkp1071. Crossref, Web of Science, Google Scholar
S. R. Viswanathanet al., Nature. Genet. 41, 843 (2009), DOI: 10.1038/ng.392. Crossref, Web of Science, Google Scholar
Y. Namet al., Cell 147, 1080 (2011), DOI: 10.1016/j.cell.2011.10.020. Crossref, Web of Science, Google Scholar
A. Desjardinset al., Nucleic. Acids. Res. 40, 1767 (2012), DOI: 10.1093/nar/gkr808. Crossref, Web of Science, Google Scholar
F. E. Loughlinet al., Nature. Struct. Biol. 19, 84 (2012), DOI: 10.1038/nsmb.2202. Crossref, Google Scholar
S. D. Auweter, F. C. Oberstrass and F. H.-T. Allain, Nucleic. Acids. Res. 34, 4943 (2006), DOI: 10.1093/nar/gkl620. Crossref, Web of Science, Google Scholar
R. P. Bahadur, M. Zacharias and J. Janin, Nucleic. Acids. Res. 36, 2705 (2008), DOI: 10.1093/nar/gkn102. Crossref, Web of Science, Google Scholar
X. Cao, C. Liu and Y. Liu, J. Theor. Comput. Chem. 11, 573 (2012), DOI: 10.1142/S021963361250037X. Link, Web of Science, Google Scholar
T. M. T. Hall, Curr. Opin. Struct. Biol. 15, 367 (2005), DOI: 10.1016/j.sbi.2005.04.004. Crossref, Web of Science, Google Scholar
J. J. Ellis, M. Broom and S. Jones, Proteins 66, 903 (2007), DOI: 10.1002/prot.21211. Crossref, Web of Science, Google Scholar
N. Morozovaet al., Bioinformatics 22, 2746 (2006), DOI: 10.1093/bioinformatics/btl470. Crossref, Web of Science, Google Scholar
A. Gupta and M. Gribskov, J. Mol. Biol. 409, 574 (2011), DOI: 10.1016/j.jmb.2011.04.007. Crossref, Web of Science, Google Scholar
S. Liet al., J. Theor. Comput. Chem. 11, 329 (2012), DOI: 10.1142/S021963361250023X. Link, Web of Science, Google Scholar
D. A. Caseet al., AMBER 11, (2008). Google Scholar
K. Gao and M. Yang, J. Theor. Comput. Chem. 11, 1201 (2012), DOI: 10.1142/S0219633612500800. Link, Web of Science, Google Scholar
Y. Duanet al., J. Comput. Chem. 24, 1999 (2003), DOI: 10.1002/jcc.10349. Crossref, Web of Science, Google Scholar
W. L. Jorgensenet al., J. Chem. Phys. 79, 926 (1983), DOI: 10.1063/1.445869. Crossref, Web of Science, Google Scholar
P.-H. Qinet al., J. Theor. Comput. Chem. 11, 1183 (2012), DOI: 10.1142/S0219633612500794. Link, Web of Science, Google Scholar
W. F. Liet al., J. Am. Chem. Soc. 130, 892 (2008), DOI: 10.1021/ja075302g. Crossref, Web of Science, Google Scholar
Y. Pang, J. Mol. Biol. 5, 196 (1999). Web of Science, Google Scholar
J. Lee, J. S. Kim and C. Seok, J. Phys. Chem. B. 114, 7662 (2010), DOI: 10.1021/jp1017289. Crossref, Web of Science, Google Scholar
A. Onufriev, D. Bashford and D. A. Case, Proteins 55, 383 (2004), DOI: 10.1002/prot.20033. Crossref, Web of Science, Google Scholar

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Vol. 12, No. 08

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Received 28 June 2013

Accepted 13 August 2013

Published: 16 October 2013

Keywords