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I know that B-conformation DNA is a right-handed helix, and most proteins that form helices form right-handed, not left-handed, helices (1). Furthermore, "Many transcription factors have an alpha-helix that binds to DNA bases in a specific fashion" (2), indicating that it is common for right-handed protein helices to bind to right-handed B-DNA helices.

Does this mean that, generally speaking, from the perspective of basic geometry, do right-handed helices bind to right- (but not left-)handed helices? And, vice versa, that left-handed helices generally bind to left- (but not right-)handed helices?

References

  1. Novotny, M., & Kleywegt, G. J. (2005). A Survey of Left-handed Helices in Protein Structures. Journal of Molecular Biology, 347(2), 231–241. https://doi.org/10.1016/J.JMB.2005.01.037
  2. Suzuki, M., & Gerstein, M. (1995). Binding geometry of alpha-helices that recognize DNA. Proteins, 23(4), 525–535. https://doi.org/10.1002/PROT.340230407
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  • $\begingroup$ But the paper you quote shows that left-handed helices in proteins only span a single turn, so fair comparison with right-handed helices is not possible. The question seems to be a case of “if left-handed helices existed”, in which case it would seem a mathematical question. $\endgroup$
    – David
    Mar 29 at 20:29
  • $\begingroup$ @David, I'm talking about dsDNA and dsRNA duplexes in the Z-conformation, a left-handed double helix, in association with the neurofibrillary tangle paired helical filaments of tau proteins, and the amyloid-beta fibrils from Alzheimer's disease patients' brains, both of which are pairs of protofilaments with a left twist. See references in my other comment: $\endgroup$
    – OdinTheDO
    Apr 14 at 17:14
  • $\begingroup$ Yang, Y. et al., (2022). Cryo-EM structures of amyloid-β 42 filaments from human brains. Science, 375, 167–172. Wischik, C. M., et al., (1985). Subunit structure of paired helical filaments in Alzheimer’s disease. The Journal of Cell Biology, 100(6), 1905–1912. doi.org/10.1083/JCB.100.6.1905 $\endgroup$
    – OdinTheDO
    Apr 14 at 17:19

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My understanding is that protein and DNA helices show the handedness that they do due largely to the intrinsic chirality of their components. Note that in natural biomolecules L-amino acids and D-sugars predominate. This apparently leads to a subsequent bias in their respective polymers.

I believe that it has been demonstrated that artificial alpha helices constructed of achiral amino acids demonstrate inversions between left and right handed forms- these then need to be stapled with extra molecular bridges to hold left or right handed orientation.

Thus, I don't think that there is a right-to-right or left-to-left association. In all cases, I think it's just that the biased handedness is baked into the structure of natural amino acids.

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  • $\begingroup$ Thanks, @Maximilian Press. What you're saying is true, but that's not really my question. I am NOT asking whether nuceic acids and proteins usually adopt right-handed helices because this makes it easier for them to bind to each other (nor am I suggesting this). I am simply asking, do right-handed helices bind more easily with other right-handed helices, and do left-handed helices tend to bind more readily and tightly with other left-handed helices? I'm being a bit coy because I don't want to give away my hypothesis, but I'm more interested in the LEFT-handed nucleic acid and protein helices. $\endgroup$
    – OdinTheDO
    Mar 29 at 17:14
  • $\begingroup$ @OdinTheDO I see. I would be interested in whether anyone had any data either way, but my guess on this is a solid "no". I think that the secondary structure of helical geometry of DNA and protein with respect to each other is probably low/no relevance for binding compared to the tertiary and quaternary structures. But that's purely a guess. $\endgroup$ Mar 29 at 18:29

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