Chemically controlled self-assembly of protein nanorings.
The exploitation of biological macromolecules, such as nucleic acids, for the fabrication of advanced materials is a promising area of research. Although a greater variety of structural and functional uses can be envisioned for protein-based materials, systematic approaches for their construction have yet to emerge. Consistent with theoretical models of polymer macrocyclization, we have demonstrated that, in the presence of dimeric methotrexate (bisMTX), wild-type Escherichia coli dihydrofolate reductase (DHFR) molecules tethered together by a flexible peptide linker (ecDHFR(2)) are capable of spontaneously forming highly stable cyclic structures with diameters ranging from 8 to 20 nm. The nanoring size is dependent on the length and composition of the peptide linker, on the affinity and conformational state of the dimerizer, and on induced protein-protein interactions. Delineation of these and other rules for the control of protein oligomer assembly by chemical induction provides an avenue to the future design of protein-based materials and nanostructures.
Carlson
Jonathan C T
JC
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Jena
Sidhartha S
SS
Flenniken
Michelle
M
Chou
Tsui-fen
TF
Siegel
Ronald A
RA
Wagner
Carston R
CR
D001665:Binding Sites; D002850:Chromatography, Gel; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D008727:Methotrexate / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D008962:Models, Theoretical; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D010455:Peptides; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate