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Title: Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening

Authors:
; ; ; ;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1398078
Grant/Contract Number:
AC02-06CH11357
Resource Type:
Journal Article: Published Article
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 24; Journal Issue: 10; Related Information: CHORUS Timestamp: 2017-10-05 09:15:51; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Ng, Leo C. T., Putrenko, Igor, Baronas, Victoria, Van Petegem, Filip, and Accili, Eric A.. Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening. United Kingdom: N. p., 2016. Web. doi:10.1016/j.str.2016.06.024.
Ng, Leo C. T., Putrenko, Igor, Baronas, Victoria, Van Petegem, Filip, & Accili, Eric A.. Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening. United Kingdom. doi:10.1016/j.str.2016.06.024.
Ng, Leo C. T., Putrenko, Igor, Baronas, Victoria, Van Petegem, Filip, and Accili, Eric A.. 2016. "Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening". United Kingdom. doi:10.1016/j.str.2016.06.024.
@article{osti_1398078,
title = {Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening},
author = {Ng, Leo C. T. and Putrenko, Igor and Baronas, Victoria and Van Petegem, Filip and Accili, Eric A.},
abstractNote = {},
doi = {10.1016/j.str.2016.06.024},
journal = {Structure},
number = 10,
volume = 24,
place = {United Kingdom},
year = 2016,
month =
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.str.2016.06.024

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  • We have studied the content of nucleic acid fragments in rabbit tissues. In the liver, spleen, appendix, bone marrow, and mucosa of the small intestine we have found adenine, guanine, hypoxanthine, uracil, and the corresponding nucleosides and nucleotides, with the latter predominating in quantitative ratio. In blood, only adenylic acid is present in appreciable concentration. We have irradiated rabbits in doses of 1000 r and this causes changes in the quantitative (oaposition of these substances. In the liver, appendix, spleen, and bone marrow, the uridylic acid content increased and in a number of cases cytidylic acid, not present in themore » normal case, appeared. in the last two tissues the uridine content decreased. In the mucosa of the small intestine the uridylic acid content fell and the uridine content rose. Among the purine derivatives the greatest change was shown by inosine (it increased in liver and appendix, decreased in spleen), adenosine (rose in liver, fall in spleen and bone marrow), adenylic acid (increased in liver), and hypoxanthine (increased in liver, decreased in spleen). We have presented a possible mechanism for the change in nucleic acid fragments. (auth)« less
  • Detailed conformation and dynamics of heterodinucleoside monophosphates have been studied by nuclear magnetic resonance. Ribose rings exist as equilibrium mixtures of C(2')-endo(/sup 2/E) reversible C(3')-endo(/sup 3/E) conformers with a proclivity for the /sup 3/E pucker; C(4')-C(5') bonds show preference for a gg conformation and the dominant conformer about C(5')-O(5') is g'g'. Orientation about the C(3')-O(3') bond is coupled to the ribose conformational equilibrium and the system exists with a bias for the /sup 3/Eg/sup -/ coupled conformation in which H(3')-C(3')-O(3')-P dihedral angle occupies the narrow range of 33-35/sup 0/. Dimerization causes about 10% increase in gg and g'g' populations andmore » the g/sup -/ domain becomes increasingly populated about the C(3')-O(3') bond. The ribose equilibrium /sup 2/E reversible /sup 3/E shifts to /sup 3/E upon dimerization, especially for the pu-py series and less so for the py-pu systems suggesting a correlation between sequence and ribose conformational equilibrium. Temperature and dimerization data show the transition /sup 2/E..-->.. /sup 3/E is related to /sub chi CN/ changes induced by dimerization and stacking. Ribose coupling data show that the percentage populations of stacked species vary with GpC displaying a maximum of 45% stacked population and UpG about 10%. The pu-py dimers show a higher preference for stacked conformations than py-pu dimers. The pronounced deshielding of H(5') of the 5'-nucleotidyl units on dimerization may be associated with right-handed stacks (g/sup -/g/sup -/), whereas chemical shift trends of H(5') and H(5'') of 3'-nucleotidyl units are due to left-handed stacks (g/sup +/g/sup +/). In pu-py dimers, the population of g/sup -/g/sup -/ is greater than that of g/sup +/g/sup +/. The population of g/sup -/g/sup -/ stacks in pu-py dimers is greater than in corresponding matched py-pu dimers.« less
  • The catabolite activator protein (CAP) bends DNA in the CAP-DNA complex, typically introducing a sharp DNA kink, with a roll angle of {approx}40 deg and a twist angle of {approx}20 deg, between positions 6 and 7 of the DNA half-site, 5'-A1A2A3T4G5T6G7A8T9C10T11-3' ('primary kink'). In previous work, we showed that CAP recognizes the nucleotide immediately 5' to the primary-kink site, T6, through an 'indirect-readout' mechanism involving sequence effects on energetics of primary-kink formation. Here, to understand further this example of indirect readout, we have determined crystal structures of CAP-DNA complexes containing each possible nucleotide at position 6. The structures show thatmore » CAP can introduce a DNA kink at the primary-kink site with any nucleotide at position 6. The DNA kink is sharp with the consensus pyrimidine-purine step T{sub 6}G{sub 7}, and the non-consensus pyrimidine-purine step C{sub 6}G{sub 7} (roll angles of {approx}42 deg, twist angles of {approx}16 deg), but is much less sharp with the non-consensus purine-purine steps A{sub 6}G{sub 7} and G{sub 6}G{sub 7} (roll angles of {approx}20 deg, twist angles of {approx}17 deg). We infer that CAP discriminates between consensus and non-consensus pyrimidine-purine steps at positions 6-7 solely based on differences in the energetics of DNA deformation, but that CAP discriminates between the consensus pyrimidine-purine step and non-consensus purine-purine steps at positions 6-7 both based on differences in the energetics of DNA deformation and based on qualitative differences in DNA deformation. The structures further show that CAP can achieve a similar, {approx}46 deg per DNA half-site, overall DNA bend through a sharp DNA kink, a less sharp DNA kink, or a smooth DNA bend. Analysis of these and other crystal structures of CAP-DNA complexes indicates that there is a large, {approx}28 deg per DNA half-site, out-of-plane component of CAP-induced DNA bending in structures not constrained by end-to-end DNA lattice interactions and that lattice contacts involving CAP tend to involve residues in or near biologically functional surfaces.« less
  • The authors have investigated the structure and physical chemistry of the d(C{sub 3}T{sub 4}C{sub 3}){center dot}2(d(G{sub 3}A{sub 4}G{sub 3})) triple helix by polyacrylamide gel electrophoresis (PAGE), {sup 1}H NMR, and ultraviolet (UV) absorption spectroscopy. The triplex was stabilized with MgCl{sub 2} at neutral pH. PAGE studies verify the stoichiometry of the strands comprising the triplex and indicate that the orientation of the third strand in purine-purine-pyrimidine (pur-pur-pyr) triplexes is antiparallel with respect to the purine strand of the underlying duplex. Imino proton NMR spectra provide evidence for the existence of new purine-purine (pur{center dot}pur) hydrogen bonds, in addition to thosemore » of the Watson-Crick (W-C) base pairs, in the triplex structure. These new hydrogen bonds are likely to correspond to the interaction between third-strand guanine NH1 imino protons and the N7 atoms of guanine residues on the puring strand of the underlying duplex. Thermal denaturation of the triplex proceeds to single strands in one step, under the conditions used in this study. Binding of the third strand appears to enhance the thermal stability of the duplex by 1-3 C, depending on the DNA concentration. This marked enhancement in stability, coupled with the lack of an acidic pH requirement, suggests that pur-pur-pyr triplexes are appealing choices for use in applications involving oligonucleotide targeting of duplex DNA in vitro and in vivo.« less