Protein camouflage in cytochrome c–calixarene complexes

Abstract

Small molecules that recognize protein surfaces are important tools for modifying protein interaction properties. Since the 1980s, several thousand studies concerning calixarenes and host-guest interactions have been published. Although there is growing interest in protein-calixarene interactions, only limited structural information has been available to date. We now report the crystal structure of a protein-calixarene complex. The water-soluble p-sulfonatocalix[4]arene is shown to bind the lysine-rich cytochrome c at three different sites. Binding curves obtained from NMR titrations reveal an interaction process that involves two or more binding sites. Together, the data indicate a dynamic complex in which the calixarene explores the surface of cytochrome c. In addition to providing valuable information on protein recognition, the data also indicate that the calixarene is a mediator of protein-protein interactions, with potential applications in generating assemblies and promoting crystallization.

Overcoming bottlenecks in the membrane protein structural biology pipeline

“…This allowed the identification of IFITM2 as a specific partner and provided molecular clues to signalling in the context of pancreatic cancer [36]. Some calixarenes have been shown to facilitate crystallisation of proteins [35,37,38]. Significant progress has been made in generating different calixarenes with different chemical characteristics to favour solubilisation and stabilisation at the same time, to improve stability after solubilisation or to facilitate crystallisation.…”

Effects of sequence context on the binding of tryptophan-containing peptides by the cucurbit[8]uril–methyl viologen complex

“…In any case, it is important to understand how the sequence environment (i.e., neighboring residues) influences binding. Several synthetic receptors have been shown to bind peptides and proteins (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), but in the majority of cases, these receptors are known to bind to a single type of residue, and the effects of sequence context are understood to a limited extent. This paper describes the effects of sequence context on the interactions of tryptophan-containing peptides with the synthetic receptor, cucurbit [8]uril (Q8), and a method that enables this determination in a rapid and parallel fashion.…”

A synthetic nanomaterial for virus recognition produced by surface imprinting

“…Special focus has been placed on macrocyclic molecules, which have been shown to possess remarkable recognition properties with respect to anions 8 , cations 9 and small neutral molecules 10 . However, owing to a size discrepancy between host and guest molecules that is typically one to two orders of magnitude, applications with larger targets, such as proteins 2,11,12 , are limited.…”