Rational design of a reversible pH-responsive switch for peptide self-assembly.
Peptide TZ1H, based on the heptad sequence of a coiled-coil trimer, undergoes fully reversible, pH-dependent self-assembly into long-aspect-ratio helical fibers. Substitution of isoleucine residues with histidine at the core d-positions of alternate heptads introduces a mechanism by which self-assembly is coupled to the protonation state of the imidazole side chain. Circular dichroism spectroscopy, transmission electron microscopy, and microrheology techniques revealed that the self-assembly of TZ1H coincides with a distinct coil-helix conformational transition that occurs within a narrow pH range near the pKa of the imidazole side chains of the core histidine residues.
Zimenkov
Yuri
Y
Department of Chemistry and The Integrated Microscopy and Microanalytical Facility, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
Dublin
Steven N
SN
Ni
Rong
R
Tu
Raymond S
RS
Breedveld
Victor
V
Apkarian
Robert P
RP
Conticello
Vincent P
VP
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007532:Isoleucine / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
D010455:Peptides; D007532:Isoleucine; D006639:Histidine