Nicholson David A, Sengupta Abhigyan, Nesbitt David J
JILA, National Institute of Standards and Technology and University of Colorado Boulder, Boulder, Colorado 80309 United States.
Department of Chemistry, University of Colorado Boulder, Boulder, Colorado 80309, United States.
J Phys Chem B. 2020 Dec 24;124(51):11561-11572. doi: 10.1021/acs.jpcb.0c07420. Epub 2020 Dec 9.
The preponderance of a specific d- or l-chirality in fats, sugars, amino acids, nucleic acids, and so on is ubiquitous in nature, yet the biological origin of such chiral dominance (i.e., with one enantiomer overwhelmingly present) remains an open question. One plausible proposal for the predominance of l-chirality in amino acids could be through evolutionary templating of chiral RNA-folding via chaperone activity. To help evaluate this possibility, single molecule fluorescence experiments have been performed that measure the chiral dependence of chaperone folding dynamics for the simple tetraloop-tetraloop receptor (TL-TLR) tertiary binding motif in the presence of a series of chiral amino acids. Specifically, d- vs l-arginine is found to accelerate the unfolding of this RNA motif in a chirally selective fashion, with temperature-dependent studies of the kinetics performed to extract free energy, enthalpy, and entropy landscapes for the underlying thermodynamics. Furthermore, all-atom molecular dynamics (MD) simulations are pursued to provide additional physical insight into this chiral sensitivity, which reveal enantiomer-specific sampling of nucleic acid surfaces by d- vs l-arginine and support a putative mechanism for chirally specific denaturation of RNA tertiary structure by arginine but not other amino acids.
在脂肪、糖类、氨基酸、核酸等物质中，特定的d型或l型手性占优势的情况在自然界中普遍存在，然而这种手性优势（即一种对映体大量存在）的生物学起源仍然是一个悬而未决的问题。关于氨基酸中l型手性占优势的一个合理推测可能是通过伴侣活性对手性RNA折叠进行进化模板化。为了评估这种可能性，已经进行了单分子荧光实验，这些实验测量了在一系列手性氨基酸存在下，简单四环-四环受体（TL-TLR）三级结合基序的伴侣折叠动力学的手性依赖性。具体而言，发现d-精氨酸与l-精氨酸以手性选择性方式加速这种RNA基序的解折叠，并进行了动力学的温度依赖性研究，以提取基础热力学的自由能、焓和熵景观。此外，还进行了全原子分子动力学（MD）模拟，以提供对这种手性敏感性的额外物理见解，模拟结果揭示了d-精氨酸与l-精氨酸对核酸表面进行对映体特异性采样，并支持精氨酸而非其他氨基酸对RNA三级结构进行手性特异性变性的推测机制。
