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Non-Conserved Amino Acid Residues Modulate the Thermodynamics of Zn(II) Binding to Classical ββα Zinc Finger Domains.
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- Additional Information
- Source:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
- Publication Information:
Original Publication: Basel, Switzerland : MDPI, [2000-
- Subject Terms:
- Abstract:
Classical zinc fingers domains (ZFs) bind Zn(II) ion by a pair of cysteine and histidine residues to adopt a characteristic and stable ββα fold containing a small hydrophobic core. As a component of transcription factors, they recognize specific DNA sequences to transcript particular genes. The loss of Zn(II) disrupts the unique structure and function of the whole protein. It has been shown that the saturation of ZFs under cellular conditions is strictly related to their affinity for Zn(II). High affinity warrants their constant saturation, while medium affinity results in their transient structurization depending on cellular zinc availability. Therefore, there must be factors hidden in the sequence and structure of ZFs that impact Zn(II)-to-protein affinities to control their function. Using molecular dynamics simulations and experimental spectroscopic and calorimetric approaches, we showed that particular non-conserved residues derived from ZF sequences impact hydrogen bond formation. Our in silico and in vitro studies show that non-conserved residues can alter metal-coupled folding mechanisms and overall ZF stability. Furthermore, we show that Zn(II) binding to ZFs can also be entropically driven. This preference does not correlate either with Zn(II) binding site or with the extent of the secondary structure but is strictly related to a reservoir of interactions within the second coordination shell, which may loosen or tighten up the structure. Our findings shed new light on how the functionality of ZFs is modulated by non-coordinating residues diversity under cellular conditions. Moreover, they can be helpful for systematic backbone alteration of native ZF ββα scaffold to create artificial foldamers and proteins with improved stability.
- References:
J Comput Chem. 2005 Dec;26(16):1701-18. (PMID: 16211538)
J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254)
Adv Drug Deliv Rev. 2009 Jul 2;61(7-8):513-26. (PMID: 19394375)
Org Lett. 2012 Feb 3;14(3):732-5. (PMID: 22257322)
Arch Biochem Biophys. 2016 Dec 1;611:3-19. (PMID: 27117234)
Inorg Chem. 2003 Mar 24;42(6):1994-2003. (PMID: 12639134)
Bioinformatics. 2006 Nov 1;22(21):2695-6. (PMID: 16940322)
Anal Chem. 2013 Dec 3;85(23):11479-86. (PMID: 24180305)
Inorg Chem. 2011 Jan 3;50(1):72-85. (PMID: 21141850)
Biochemistry. 1992 Aug 25;31(33):7463-76. (PMID: 1510933)
Biochemistry. 2000 Apr 18;39(15):4327-38. (PMID: 10757981)
Phys Chem Chem Phys. 2009 Feb 14;11(6):975-83. (PMID: 19177216)
ACS Chem Biol. 2014 Aug 15;9(8):1662-7. (PMID: 24936957)
Trends Biochem Sci. 2021 Jan;46(1):64-79. (PMID: 32958327)
Nat Struct Biol. 1996 Nov;3(11):940-5. (PMID: 8901872)
Metallomics. 2014 Nov;6(11):2015-24. (PMID: 25109667)
J Mol Graph. 1996 Feb;14(1):33-8, 27-8. (PMID: 8744570)
Curr Opin Struct Biol. 2001 Apr;11(2):224-30. (PMID: 11297932)
Protein Eng. 2002 Jan;15(1):29-33. (PMID: 11842235)
J Cell Biochem. 2015 Nov;116(11):2435-44. (PMID: 25989233)
J Mol Biol. 2005 Dec 2;354(3):507-19. (PMID: 16253273)
J Mol Biol. 2002 Mar 1;316(4):969-89. (PMID: 11884136)
Protein Sci. 2004 Dec;13(12):3115-26. (PMID: 15557258)
Biophys J. 1993 Mar;64(3):749-53. (PMID: 8471726)
Acc Chem Res. 2014 Aug 19;47(8):2309-18. (PMID: 24877793)
Acc Chem Res. 2018 May 15;51(5):1220-1228. (PMID: 29672021)
Metallomics. 2018 Dec 12;10(12):1755-1776. (PMID: 30358795)
J Chem Inf Model. 2019 Sep 23;59(9):3803-3816. (PMID: 31385702)
Sci Rep. 2016 Nov 03;6:36346. (PMID: 27808280)
Mol Biosyst. 2016 Apr;12(4):1183-93. (PMID: 26936488)
J Chem Phys. 2010 May 28;132(20):205101. (PMID: 20515113)
J Inorg Biochem. 2020 Mar;204:110955. (PMID: 31841759)
Proteins. 1999 Mar 1;34(4):497-507. (PMID: 10081962)
J Am Chem Soc. 2008 Jan 23;130(3):892-900. (PMID: 18163620)
Proteins. 1998 Nov 1;33(2):159-66. (PMID: 9779785)
Int J Mol Sci. 2017 Oct 31;18(11):. (PMID: 29088067)
J Mol Graph Model. 2009 Jun-Jul;27(8):889-99. (PMID: 19264523)
Protein Eng. 1999 Aug;12(8):635-8. (PMID: 10469823)
J Am Chem Soc. 2012 Jun 27;134(25):10405-18. (PMID: 22591173)
J Am Chem Soc. 2017 Jun 14;139(23):7931-7938. (PMID: 28509549)
J Biol Inorg Chem. 2006 Nov;11(8):1049-62. (PMID: 16924557)
Metallomics. 2018 Feb 21;10(2):248-263. (PMID: 29230465)
Nat Methods. 2019 Aug;16(8):670-673. (PMID: 31363226)
Biochemistry. 2002 Dec 17;41(50):15068-73. (PMID: 12475256)
Eur J Biochem. 1994 Dec 1;226(2):277-83. (PMID: 8001545)
Front Mol Biosci. 2021 Sep 30;8:696609. (PMID: 34660691)
Chem Commun (Camb). 2013 Feb 14;49(13):1312-4. (PMID: 23303248)
J Am Chem Soc. 2021 Oct 13;143(40):16486-16501. (PMID: 34477370)
J Am Chem Soc. 2010 Dec 22;132(50):17760-74. (PMID: 21105707)
J Am Chem Soc. 2007 Oct 24;129(42):12815-27. (PMID: 17902663)
- Grant Information:
2018/31/B/NZ1/00567 National Science Center
- Contributed Indexing:
Keywords: DNA; energetics; hydrogen bond; isothermal titration calorimetry; metal binding affinity; metal-coupled folding; molecular dynamics
- Accession Number:
0 (Amino Acids)
J41CSQ7QDS (Zinc)
- Publication Date:
Date Created: 20221211 Date Completed: 20221216 Latest Revision: 20221221
- Publication Date:
20240829
- Accession Number:
PMC9735795
- Accession Number:
10.3390/ijms232314602
- Accession Number:
36498928
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