TY - JOUR
T1 - Protein Dimerization on a Phosphonated Calix[6]arene Disc
AU - Rennie, Martin
AU - Doolan, Aishling
AU - Raston, Colin
AU - Crowley, Peter
AU - Crowley, Peter
PY - 2017/5/8
Y1 - 2017/5/8
N2 - Complex formation between cationic cytochrome c and the water-soluble, poly-anionic p-phosphonatocalix[6]arene (pclx6) was investigated. A crystal structure (at 1.8 Å resolution) revealed a remarkable dimeric disc of pclx6 that acts like glue to mediate a symmetric (C2) protein dimer. The calixarene disc has a diameter of about 1.5 nm and masks about 360 Å2 of protein surface. The key protein–calixarene contacts occur via two linchpin lysines, with additional contacts provided by a small hydrophobic patch. The protein–calixarene supramolecular assemblies were observed in solution by size-exclusion chromatography with multi-angle light scattering and NMR spectroscopy. Using isothermal titration calorimetry and NMR data, an apparent Kd in the low micromolar range was determined for the charge-rich protein–calixarene complex. In contrast to p-sulfonatocalix[4]arene, the larger pclx6 has a single, well-defined binding site that mediates the assembly of cytochrome c in solution.
AB - Complex formation between cationic cytochrome c and the water-soluble, poly-anionic p-phosphonatocalix[6]arene (pclx6) was investigated. A crystal structure (at 1.8 Å resolution) revealed a remarkable dimeric disc of pclx6 that acts like glue to mediate a symmetric (C2) protein dimer. The calixarene disc has a diameter of about 1.5 nm and masks about 360 Å2 of protein surface. The key protein–calixarene contacts occur via two linchpin lysines, with additional contacts provided by a small hydrophobic patch. The protein–calixarene supramolecular assemblies were observed in solution by size-exclusion chromatography with multi-angle light scattering and NMR spectroscopy. Using isothermal titration calorimetry and NMR data, an apparent Kd in the low micromolar range was determined for the charge-rich protein–calixarene complex. In contrast to p-sulfonatocalix[4]arene, the larger pclx6 has a single, well-defined binding site that mediates the assembly of cytochrome c in solution.
KW - cytochrome c
KW - lysine recognition
KW - polyanions
KW - self-assembly
KW - structure elucidation
UR - https://doi.org/10.1002/anie.201701500
UR - http://www.scopus.com/inward/record.url?scp=85017519589&partnerID=8YFLogxK
U2 - 10.1002/anie.201701500
DO - 10.1002/anie.201701500
M3 - Article
SN - 1433-7851
VL - 56
SP - 5517
EP - 5521
JO - Angewandte Chemie-International Edition
JF - Angewandte Chemie-International Edition
IS - 20
ER -