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Special Issue "Biophysical Characterization and Molecular Engineering of Multidomain Proteins"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: 30 November 2020.

Special Issue Editors

Prof. Dr. Koichi Kato
Website
Guest Editor
Department of Creative Research, Biomolecular Organization Research Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, Okazaki, Japan
Interests: biomolecular ordering; glycobiophysics; biomolecular NMR spectroscopy
Special Issues and Collections in MDPI journals
Prof. Dr. Takayuki Uchihashi
Website
Guest Editor
Laboratory of Biomolecular Dynamics and Function, Department of Physics, Nagoya University, Nagoya, Japan
Interests: single-molecule biophysics; protein dynamics; protein assembly; atomic force microscopy; optical microscopy

Special Issue Information

Dear Colleagues,

Most proteins working in living systems consist of evolutionarily acquired multiple domains, which cooperate with one another and exhibit synergistic actions, thereby exerting sophisticated functions typified by allosteric regulations. Structural proteomics, in conjunction with bioinformatics, have achieved systematic classification and the prediction of tertiary structures of individual domains as globular structural units. However, it remains challenging to delineate or predict the overall conformations of multidomain proteins, primarily because of their dynamic properties. In this class of proteins, the globular domains are connected through flexible linkers, and, consequently, are mobile to a greater or lesser extent, which enables variable spatial arrangements of the domains, depending on their cognate ligands or binding partners, as well as solution conditions such as pH. Therefore, to elucidate the mechanisms underlying multidomain protein functions, applications of experimental and theoretical methods are necessary in order to provide dynamic views of domain–domain interactions. This line of approach will offer a structural basis for the design and engineering of multidomain proteins.

As the guest editors of this Special Issue, titled “Biophysical Characterization and Molecular Engineering of Multidomain Proteins”, in IJMS, we welcome contributions from various research fields, including biophysics, bioinformatics, biomolecular engineering, and molecular phylogenetics. Formats for submissions include original research reports, reviews/mini-reviews, perspectives/opinions, and methodology articles.

Prof. Dr. Koichi Kato
Prof. Dr. Takayuki Uchihashi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (4 papers)

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Research

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Open AccessArticle
An EPR Study on the Interaction between the Cu(I) Metal Binding Domains of ATP7B and the Atox1 Metallochaperone
Int. J. Mol. Sci. 2020, 21(15), 5536; https://doi.org/10.3390/ijms21155536 - 02 Aug 2020
Abstract
Copper’s essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper [...] Read more.
Copper’s essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper trafficking mechanism in humans, by considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains of ATP7B. Our study revealed that Cu(I) is most likely mediated by the binding of the Atox1 monomer to metal binding domain 1 (MBD1) and MBD4 of ATP7B in the final part of its extraction pathway, while the other MBDs mediate this interaction and participate in copper transfer between the various MBDs to the ATP7B membrane domain. This research also proposes that MBD1-3 and MBD4-6 act as two independent units. Full article
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Open AccessArticle
NMR Characterization of Conformational Interconversions of Lys48-Linked Ubiquitin Chains
Int. J. Mol. Sci. 2020, 21(15), 5351; https://doi.org/10.3390/ijms21155351 - 28 Jul 2020
Abstract
Ubiquitin (Ub) molecules can be enzymatically connected through a specific isopeptide linkage, thereby mediating various cellular processes by binding to Ub-interacting proteins through their hydrophobic surfaces. The Lys48-linked Ub chains, which serve as tags for proteasomal degradation, undergo conformational interconversions between open and [...] Read more.
Ubiquitin (Ub) molecules can be enzymatically connected through a specific isopeptide linkage, thereby mediating various cellular processes by binding to Ub-interacting proteins through their hydrophobic surfaces. The Lys48-linked Ub chains, which serve as tags for proteasomal degradation, undergo conformational interconversions between open and closed states, in which the hydrophobic surfaces are exposed and shielded, respectively. Here, we provide a quantitative view of such dynamic processes of Lys48-linked triUb and tetraUb in solution. The native and cyclic forms of Ub chains are prepared with isotope labeling by in vitro enzymatic reactions. Our comparative NMR analyses using monomeric Ub and cyclic diUb as reference molecules enabled the quantification of populations of the open and closed states for each Ub unit of the native Ub chains. The data indicate that the most distal Ub unit in the Ub chains is the most apt to expose its hydrophobic surface, suggesting its preferential involvement in interactions with the Ub-recognizing proteins. We also demonstrate that a mutational modification of the distal end of the Ub chain can remotely affect the solvent exposure of the hydrophobic surfaces of the other Ub units, suggesting that Ub chains could be unique design frameworks for the creation of allosterically controllable multidomain proteins. Full article
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Open AccessArticle
An Off-the-Shelf Approach for the Production of Fc Fusion Proteins by Protein Trans-Splicing towards Generating a Lectibody In Vitro
Int. J. Mol. Sci. 2020, 21(11), 4011; https://doi.org/10.3390/ijms21114011 - 03 Jun 2020
Abstract
Monoclonal antibodies, engineered antibodies, and antibody fragments have become important biological therapeutic platforms. The IgG format with bivalent binding sites has a modular structure with different biological roles, i.e., effector and binding functions, in different domains. We demonstrated the reconstruction of an IgG-like [...] Read more.
Monoclonal antibodies, engineered antibodies, and antibody fragments have become important biological therapeutic platforms. The IgG format with bivalent binding sites has a modular structure with different biological roles, i.e., effector and binding functions, in different domains. We demonstrated the reconstruction of an IgG-like domain structure in vitro by protein ligation using protein trans-splicing. We produced various binding domains to replace the binding domain of IgG from Escherichia coli and the Fc domain of human IgG from Brevibacillus choshinensis as split-intein fusions. We showed that in vitro protein ligation could produce various Fc-fusions at the N-terminus in vitro from the independently produced domains from different organisms. We thus propose an off-the-shelf approach for the combinatorial production of Fc fusions in vitro with several distinct binding domains, particularly from naturally occurring binding domains. Antiviral lectins from algae are known to inhibit virus entry of HIV and SARS coronavirus. We demonstrated that a lectin could be fused with the Fc-domain in vitro by protein ligation, producing an IgG-like molecule as a “lectibody”. Such an Fc-fusion could be produced in vitro by this approach, which could be an attractive method for developing potential therapeutic agents against rapidly emerging infectious diseases like SARS coronavirus without any genetic fusion and expression optimization. Full article
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Review

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Open AccessReview
Roles of Membrane Domains in Integrin-Mediated Cell Adhesion
Int. J. Mol. Sci. 2020, 21(15), 5531; https://doi.org/10.3390/ijms21155531 - 01 Aug 2020
Abstract
The composition and organization of the plasma membrane play important functional and regulatory roles in integrin signaling, which direct many physiological and pathological processes, such as development, wound healing, immunity, thrombosis, and cancer metastasis. Membranes are comprised of regions that are thick or [...] Read more.
The composition and organization of the plasma membrane play important functional and regulatory roles in integrin signaling, which direct many physiological and pathological processes, such as development, wound healing, immunity, thrombosis, and cancer metastasis. Membranes are comprised of regions that are thick or thin owing to spontaneous partitioning of long-chain saturated lipids from short-chain polyunsaturated lipids into domains defined as ordered and liquid-disorder domains, respectively. Liquid-ordered domains are typically 100 nm in diameter and sometimes referred to as lipid rafts. We posit that integrin β senses membrane thickness and that mechanical force on the membrane regulates integrin activation through membrane thinning. This review examines what we know about the nature and mechanism of the interaction of integrins with the plasma membrane and its effects on regulating integrins and its binding partners. Full article
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