Defining the Structure of a Protein–Spherical
Nucleic Acid Conjugate and Its Counterionic Cloud
Version 3 2018-03-28, 04:13
Version 2 2018-03-13, 13:50
Version 1 2018-03-13, 12:51
Posted on 2018-03-28 - 04:13
Protein–spherical nucleic
acid conjugates (Pro-SNAs) are
an emerging class of bioconjugates that have properties defined by
their protein cores and dense shell of oligonucleotides. They have
been used as building blocks in DNA-driven crystal engineering strategies
and show promise as agents that can cross cell membranes and affect
both protein and DNA-mediated processes inside cells. However, ionic
environments surrounding proteins can influence their activity and
conformational stability, and functionalizing proteins with DNA substantively
changes the surrounding ionic environment in a nonuniform manner.
Techniques typically used to determine protein structure fail to capture
such irregular ionic distributions. Here, we determine the counterion
radial distribution profile surrounding Pro-SNAs dispersed in RbCl
with 1 nm resolution through in situ anomalous small-angle
X-ray scattering (ASAXS) and classical density functional theory (DFT).
SAXS analysis also reveals the radial extension of the DNA and the
linker used to covalently attach the DNA to the protein surface. At
the experimental salt concentration of 50 mM RbCl, Rb+ cations
compensate ∼90% of the negative charge due to the DNA and linker.
Above 75 mM, DFT calculations predict overcompensation of the DNA
charge by Rb+. This study suggests a method for exploring
Pro-SNA structure and function in different environments through predictions
of ionic cloud densities as a function of salt concentration, DNA
grafting density, and length. Overall, our study demonstrates that
solution X-ray scattering combined with DFT can discern counterionic
distribution and submolecular features of highly charged, complex
nanoparticle constructs such as Pro-SNAs and related nucleic acid
conjugate materials.
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Krishnamoorthy, Kurinji; Hoffmann, Kyle; Kewalramani, Sumit; Brodin, Jeffrey D.; Moreau, Liane M.; Mirkin, Chad A.; et al. (2018). Defining the Structure of a Protein–Spherical
Nucleic Acid Conjugate and Its Counterionic Cloud. ACS Publications. Collection. https://doi.org/10.1021/acscentsci.7b00577
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AUTHORS (8)
KK
Kurinji Krishnamoorthy
KH
Kyle Hoffmann
SK
Sumit Kewalramani
JB
Jeffrey D. Brodin
LM
Liane M. Moreau
CM
Chad A. Mirkin
MO
Monica Olvera de la Cruz
MB
Michael J. Bedzyk