Steven Boxer, Doctoral Dissertation Advisor (AC)
Dynamic Reorganization and Correlation among Lipid Raft Components.
Journal of the American Chemical Society
2016; 138 (31): 9996-10001
Lipid rafts are widely believed to be an essential organizational motif in cell membranes. However, direct evidence for interactions among lipid and/or protein components believed to be associated with rafts is quite limited owing, in part, to the small size and intrinsically dynamic interactions that lead to raft formation. Here, we exploit the single negative charge on the monosialoganglioside GM1, commonly associated with rafts, to create a gradient of GM1 in response to an electric field applied parallel to a patterned supported lipid bilayer. The composition of this gradient is visualized by imaging mass spectrometry using a NanoSIMS. Using this analytical method, added cholesterol and sphingomyelin, both neutral and not themselves displaced by the electric field, are observed to reorganize with GM1. This dynamic reorganization provides direct evidence for an attractive interaction among these raft components into some sort of cluster. At steady state we obtain an estimate for the composition of this cluster.
View details for DOI 10.1021/jacs.6b05540
View details for PubMedID 27447959
Chemical Synthesis and Self-Assembly of a Ladderane Phospholipid
J. Am. Chem. Soc.
2016; 138 (49): 15845–15848
View details for DOI 10.1021/jacs.6b10706
Atomic Recombination in Dynamic Secondary Ion Mass Spectrometry Probes Distance in Lipid Assemblies: A Nanometer Chemical Ruler
J. Am. Chem. Soc.
2016; 138 (51): 16737–16744
View details for DOI 10.1021/jacs.6b10655
Histone Demethylase LSD1 Is a Folate-Binding Protein
2011; 50 (21): 4750-4756
Methylation of lysine residues in histones has been known to serve a regulatory role in gene expression. Although enzymatic removal of the methyl groups was discovered as early as 1973, the enzymes responsible for their removal were isolated and their mechanism of action was described only recently. The first enzyme to show such activity was LSD1, a flavin-containing enzyme that removes the methyl groups from lysines 4 and 9 of histone 3 with the generation of formaldehyde from the methyl group. This reaction is similar to the previously described demethylation reactions conducted by the enzymes dimethylglycine dehydrogenase and sarcosine dehydrogenase, in which protein-bound tetrahydrofolate serves as an accepter of the formaldehyde that is generated. We now show that nuclear extracts of HeLa cells contain LSD1 that is associated with folate. Using the method of back-scattering interferometry, we have measured the binding of various forms of folate to both full-length LSD1 and a truncated form of LSD1 in free solution. The 6R,S form of the natural pentaglutamate form of tetrahydrofolate bound with the highest affinity (K(d) = 2.8 μM) to full-length LSD1. The fact that folate participates in the enzymatic demethylation of histones provides an opportunity for this micronutrient to play a role in the epigenetic control of gene expression.
View details for DOI 10.1021/bi200247b
View details for Web of Science ID 000290837400035
View details for PubMedID 21510664