Protein Nanotube Selectively Cleavable with DNA: Supramolecular Polymerization of “DNA-Appended Molecular Chaperones”

Here, we report molecular chaperone GroELs that carry, at their apical domains, multiple DNA strands (ideally 28 DNA strands in total) with defined oligonucleotide (nt) sequences. This design strategy allows for the preparation of GroEL_10a and GroEL_10b carrying 10-nt DNA strands of 10a and 10b with complementary sequences, respectively, at their apical domains. One-dimensional coassembly of these GroELs is possible to form protein nanotube NT_10a/10b with an anomalous thermodynamic stability due to the exceptionally large multivalency for the coassembly. Likewise, comparably stable nanotube NT_15c/10d was obtained even when the apical-domain DNA strands (15c and 10d) were partially complementary to one another. Nevertheless, in sharp contrast with NT_10a/10b, NT_15c/10d, when incubated with DNA 15d, dissociates rapidly and completely because 15d preferentially hybridizes with the DNA strands of 15c in NT_15c/10d by displacing those of 10d, to afford a mixture of GroEL_15c/15d and GroEL_10d. Even in the presence of NT_10c/10d, 15d cleaved off NT_15c/10d selectively, indicating the potential utility of NTs for targeted delivery.