Use of 3D domain swapping in constructing supramolecular metalloproteins

Hirota, Shun; Mashima, Tsuyoshi; Kobayashi, Naoya

doi:10.1039/d1cc04608j

Cited by 10 publications

(5 citation statements)

References 106 publications

(171 reference statements)

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“…22 This region includes the hinge region (Lys79–Ala83) of domain swapping. 20 In our present study, the A83C variant forms a disulfide bond between Cys83 in the dimer, thereby limiting the structural flexibility around Cys83, which is located in the Pro71–Lys87 Ω loop, and inhibiting amyloid fibril formation. The Pro71–Lys87 Ω loop has been shown to change its conformation by cleavage of the heme-Met80 coordination bond.…”

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confidence: 67%

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Structural region essential for amyloid fibril formation in cytochrome c elucidated by optical trapping

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“…S3f and S4f, ESI†) are listed in Table 1. The sizes of the cyt c dimers would not significantly differ judging from the structures of the monomer and domain-swapped dimer, 5,20 leading to similar trapping efficiency and aggregation behaviours for the dimers in phase A. High concentrations of proteins are reported to be necessary for amyloid fibril formation.…”

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Structural region essential for amyloid fibril formation in cytochrome c elucidated by optical trapping

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“…In contrast, the so-called domain swapping method, in which secondary structural units are recombined among target proteins, is one of the effective methods for protein redesign [ 21 , 22 ]. We attempted to modify the DNA recognition ability of ZF proteins using the domain swap method, in which secondary structural units such as α-helix and β-hairpin of ZFs are swapped with those of other ZFs (Fig.…”

Section: Modification Of Dna Recognition Ability Of Zfs Targeting Sec...mentioning

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The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications

et al. 2023

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Zinc finger proteins are abundant in the human proteome and are responsible for a variety of functions. The domains that constitute zinc finger proteins are compact spherical structures, each comprising approximately 30 amino acid residues, but they also have precise molecular factor functions: zinc binding and DNA recognition. Due to the biological importance of zinc finger proteins and their unique structural and functional properties, many artificial zinc finger proteins have been created and are expected to improve their functions and biological applications. In this study, we review previous studies on the redesign and application of artificial zinc finger proteins, focusing on the experimental results obtained by our research group. In addition, we systematically review various design strategies used to construct artificial zinc finger proteins and discuss in detail their potential biological applications, including gene editing. This review will provide relevant information to researchers involved or interested in the field of artificial zinc finger proteins as a potential new treatment for various diseases.

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“…The structural unit of the 3D-DS oligomers mirrors the corresponding monomer structure, except for the hinge region that connects the exchanged regions. This phenomenon is common in proteins [14][15][16][17][18][19] , including several types of 3D-DS for certain antibodies. For instance, the human antibody 2G12, an HIV-1 neutralizer, can undergo 3D-DS by exchanging the heavy chain variable region between two antigen-binding (Fab) regions 20 .…”

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Structural and Thermodynamic Insights into Antibody Light Chain Tetramer Formation through 3D Domain Swapping

Hirota,

Sakai,

Mashima

et al. 2023

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Monoclonal antibodies are successfully used in the fields of pharmacy and medicine. While antibodies easily form aggregates and may lose the ability to recognize antigens, atomic-level structural examinations of antibody light chain aggregates are sparse. In this study, we present an antibody light chain that maintains an equilibrium between its monomeric and tetrameric states. According to data from X-ray crystallography, thermodynamic and kinetic measurements, as well as theoretical studies, this antibody light chain engages in 3D domain swapping within its variable region. Here, a pair of domain-swapped dimers creates a tetramer through hydrophobic interactions, facilitating the revelation of the domain-swapped structure. The negative cotton effect linked to the β-sheet structure, observed around 215 nm in the circular dichroism spectrum of the tetrameric variable region, is more pronounced than that of the monomer. This suggests that the monomer contains less β-sheet structures and exhibits greater flexibility than the tetramer in solution. These findings not only clarify the domain-swapped structure of an antibody light chain but also contribute to controlling antibody quality and advancing the development of future molecular recognition agents and drugs.

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Use of 3D domain swapping in constructing supramolecular metalloproteins

Abstract: Many metalloproteins can undergo 3D domain swapping. This future article summarizes in vitro and in vivo formation of supramolecular metalloproteins through 3D domain swapping.

Cited by 10 publications

References 106 publications

Structural region essential for amyloid fibril formation in cytochrome c elucidated by optical trapping

Structural region essential for amyloid fibril formation in cytochrome c elucidated by optical trapping

The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications

Structural and Thermodynamic Insights into Antibody Light Chain Tetramer Formation through 3D Domain Swapping

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