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1. Binding of Dipeptides to Fatty Acid Membranes Explains Their Colocalization in Protocells but Does Not Select for Them Relative to Unjoined Amino Acids

   Mengjun Xue, Roy A. (July 2021, The journal of physical chemistry)

   null (Ed.)

   Dipeptides, which consist of two amino acids joined by a peptide bond, have been shown to have catalytic functions. This observation leads to fundamental questions relevant to the origin of life. How could peptides have become colocalized with the first protocells? Which structural features would have determined the association of amino acids and peptides with membranes? Could the association of dipeptides with protocell membranes have driven molecular evolution, favoring dipeptides over individual amino acids? Using pulsed-field gradient nuclear magnetic resonance, we find that several prebiotic amino acids and dipeptides bind to prebiotic membranes. For amino acids, the side chains and carboxylate contribute to the interaction. For dipeptides, the extent of binding is generally less than that of the constituent amino acids, implying that other mechanisms would be necessary to drive molecular evolution. Nevertheless, our results are consistent with a scheme in which the building blocks of the biological polymers colocalized with protocells prior to the emergence of RNA and proteins. 

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2. Molecular investigation of the tandem Tudor domain and plant homeodomain histone binding domains of the epigenetic regulator UHRF2

   https://doi.org/10.1002/prot.26278  

   Ginnard, Shane; Winkler, Alyssa; Mellado Fritz, Carlos; Bluhm, Tatum; Kemmer, Ray; Gilliam, Marisa; Butkevich, Nick; Abdrabbo, Sara; Bricker, Kaitlyn; Feiler, Justin; et al (July 2022, Proteins)

   Dokholyan, Nikolay (Ed.)

   Ubiquitin-like containing PHD and ring finger (UHRF)1 and UHRF2 are multidomain epigenetic proteins that play a critical role in bridging crosstalk between histone modifications and DNA methylation. Both proteins contain two histone reader domains, called tandem Tudor domain (TTD) and plant homeodomain (PHD), which read the modification status on histone H3 to regulate DNA methylation and gene expression. To shed light on the mechanism of histone binding by UHRF2, we have undergone a detailed molecular investigation with the TTD, PHD and TTD-PHD domains and compared the binding activity to its UHRF1 counterpart. We found that unlike UHRF1 where the PHD is the primary binding contributor, the TTD of UHRF2 has modestly higher affinity toward the H3 tail, while the PHD has a weaker binding interaction. We also demonstrated that like UHRF1, the aromatic amino acids within the TTD are important for binding to H3K9me3 and a conserved aspartic acid within the PHD forms an ionic interaction with R2 of H3. However, while the aromatic amino acids in the TTD of UHRF1 contribute to selectivity, the analogous residues in UHRF2 contribute to both selectivity and affinity. We also discovered that the PHD of UHRF2 contains a distinct asparagine in the H3R2 binding pocket that lowers the binding affinity of the PHD by reducing a potential electrostatic interaction with the H3 tail. Furthermore, we demonstrate the PHD and TTD of UHRF2 cooperate to interact with the H3 tail and that dual domain engagement with the H3 tail relies on specific amino acids. Lastly, our data indicate that the unique stretch region in the TTD of UHRF2 can decrease the melting temperature of the TTD-PHD and represents a disordered region. Thus, these subtle but important mechanistic differences are potential avenues for selectively targeting the histone binding interactions of UHRF1 and UHRF2 with small molecules. 

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3. Probing driving forces for binding between nanoparticles and amino acids by saturation-transfer difference NMR

   https://doi.org/10.1038/s41598-020-69185-7  

   Xu, Hui; Casabianca, Leah B. (July 2020, Scientific Reports)

   Abstract As nanotechnology becomes increasingly used in biomedicine, it is important to have techniques by which to examine the structure and dynamics of biologically-relevant molecules on the surface of engineered nanoparticles. Previous work has shown that Saturation-Transfer Difference (STD)-NMR can be used to explore the interaction between small molecules, including amino acids, and the surface of polystyrene nanoparticles. Here we use STD-NMR to further explore the different driving forces that are responsible for these interactions. Electrostatic effects are probed by using zwitterionic polystyrene beads and performing STD-NMR experiments at high, low, and neutral pH, as well as by varying the salt concentration and observing the effect on the STD buildup curve. The influence of dispersion interactions on ligand-nanoparticle binding is also explored, by establishing a structure–activity relationship for binding using a series of unnatural amino acids with different lengths of hydrophobic side chains. These results will be useful for predicting which residues in a peptide are responsible for binding and for understanding the driving forces for binding between peptides and nanoparticles in future studies. 

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4. Synthesis and Characterization of Amino Acid Decyl Esters as Early Membranes for the Origins of Life

   https://doi.org/10.3390/membranes12090858  

   Lago, Isabella; Black, Lissa; Wilfinger, Maximillian; Maurer, Sarah E. (September 2022, Membranes)

   Understanding how membrane forming amphiphiles are synthesized and aggregate in prebiotic settings is required for understanding the origins of life on Earth 4 billion years ago. Amino acids decyl esters were prepared by dehydration of decanol and amino acid as a model for a plausible prebiotic reaction at two temperatures. Fifteen amino acids were tested with a range of side chain chemistries to understand the role of amino acid identity on synthesis and membrane formation. Products were analyzed using LC-MS as well as microscopy. All amino acids tested produced decyl esters, and some of the products formed membranes when rehydrated in ultrapure water. One of the most abundant prebiotic amino acids, alanine, was remarkably easy to get to generate abundant, uniform membranes, indicating that this could be a selection mechanism for both amino acids and their amphiphilic derivatives. 

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5. Using EC-STM to obtain an understanding of amino acid adsorption on Au(111)

   https://doi.org/10.1063/1.5116564  

   Phillips, Jesse_A; Boyd, K_P; Baljak, I.; Harville, L_K; Iski, Erin_V (October 2019, AIP Advances)

   With increasing interest into the origin of life as well as the advancement of medical research using nanostructured architectures, investigations into amino acid assemblies have increased heavily in the field of surface science. Amino acid self/assisted-assembly on metallic surfaces is typically investigated with Scanning Tunneling Microscopy at low temperatures and under ultra-high vacuum in order to maintain a pristine surface and to provide researchers the tools to atomically interrogate the surface. However, in doing so, results often tend to be uncertain when moving to more realistic conditions. The investigation presented focuses on the electrochemical STM study of five simple amino acids as well as two modifications of a single amino acid and the means by which they interact with Au(111). Using EC-STM under in situ conditions, the amino acids were shown to have a considerable interaction with the underlying surface. In all cases, the amino acids trapped diffusing adatoms to form islands. These findings have also been observed under UHV conditions, but this is the first demonstration of the correlation in situ. Results indicate that an increase in the molecular footprint of the amino acid had a subsequent increase in the area of the islands formed. Furthermore, by shifting from a nonpolar to polar side chain, island area also increased. By analyzing the results gathered via EC-STM, fundamental insight can be gained into not only the behavior of amino acids with the underlying surface, but also into the direct comparison of LT-UHV-STM data with imaging performed under ambient conditions. 

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