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Auto‐regulated Protein Assembly on a Supramolecular Scaffold
Author(s) -
Rennie Martin L.,
Fox Gavin C.,
Pérez Javier,
Crowley Peter B.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201807490
Subject(s) - tetramer , supramolecular chemistry , oligomer , chemistry , calixarene , supramolecular assembly , crystallography , crystal structure , protein structure , stereochemistry , biophysics , biochemistry , polymer chemistry , molecule , enzyme , organic chemistry , biology
Abstract Controlled protein assembly provides a means to regulate function. Supramolecular building blocks, including rigid macrocycles, are versatile triggers of protein assembly. Now it is shown that sulfonato‐calix[8]arene ( sclx 8 ) mediates the formation of cytochrome c tetramers in solution. This tetramer spontaneously disassembles at ≥2 equivalents of sclx 8 , providing a remarkable example of auto‐regulation. Using X‐ray crystallography the sclx 8 binding sites on cytochrome c were characterized. Crystal structures at different protein–ligand ratios reveal varying degrees (up to 35 %) of protein surface coverage by the flexible calixarene and suggest a mechanism for oligomer disassembly. The solution structure of the oligomer was characterized by small‐angle X‐ray scattering. Overall, the data indicate calixarene‐controlled protein assembly and disassembly without the requirement for a competitive inhibitor, and point to protein encapsulation by a flexible macrocycle.