7XM1

Cryo-EM structure of mTIP60-Ba (metal-ion induced TIP60 (K67E) complex with barium ions

This is a non-PDB format compatible entry.

Summary for 7XM1

• Entry DOI: 10.2210/pdb7xm1/pdb
• Related: 7EQ9
• EMDB information: 33289
• Descriptor: TIP60 K67E mutant, BARIUM ION (2 entities in total)
• Functional Keywords: artificial designed protein complex, protein cage, protein nanoparticle, metal-induced protein assembly, protein metal complex, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 60
• Total formula weight: 1075889.22

Authors

Ohara, N.,Kawakami, N.,Arai, R.,Adachi, N.,Moriya, T.,Kawasaki, M.,Miyamoto, K. (deposition date: 2022-04-24, release date: 2023-01-04, Last modification date: 2023-11-29)

Primary citation

Ohara, N.,Kawakami, N.,Arai, R.,Adachi, N.,Moriya, T.,Kawasaki, M.,Miyamoto, K.
Reversible Assembly of an Artificial Protein Nanocage Using Alkaline Earth Metal Ions.
J.Am.Chem.Soc., 145:216-223, 2023

PubMed Abstract: Protein nanocages are of increasing interest for use as drug capsules, but the encapsulation and release of drug molecules at appropriate times require the reversible association and dissociation of the nanocages. One promising approach to addressing this challenge is the design of metal-dependent associating proteins. Such designed proteins typically have Cys or His residues at the protein surface for connecting the associating proteins through metal-ion coordination. However, Cys and His residues favor interactions with soft and borderline metal ions, such as Au and Zn, classified by the hard and soft acids and bases concept, restricting the types of metal ions available to drive association. Here, we show the alkaline earth (AE) metal-dependent association of the recently designed artificial protein nanocage TIP60, which is composed of 60-mer fusion proteins. The introduction of a Glu (hard base) mutation to the fusion protein (K67E mutant) prevented the formation of the 60-mer but formed the expected cage structure in the presence of Ca, Sr, or Ba ions (hard acids). Cryogenic electron microscopy (cryo-EM) analysis indicated a Ba ion at the interface of the subunits. Furthermore, we demonstrated the encapsulation and release of single-stranded DNA molecules using this system. Our results provide insights into the design of AE metal-dependent association and dissociation mechanisms for proteins.

PubMed: 36541447
DOI: 10.1021/jacs.2c09537

Experimental method

ELECTRON MICROSCOPY (3.96 Å)