Biology subjects

Tanaka, S.-i.

Publications and source records attributed to Tanaka, S.-i..

3 recordsLinked to original sources

bioRxiv2026

Structural basis for monobody OP-4 binding to open-form adenylate kinase

Monobodies are fibronectin type-III-based binding proteins that specifically bind target proteins and regulate their functions. We previously identified monobodies that selectively recognize either the OPEN or CLOSED conformation of adenylate kinase (Adk), revealing that monobodies can discriminate distinct conformational states of a target protein. However, the molecular basis of OPEN-form recognition has remained unclear because the structure of the complex between an OPEN-form-specific monobody and Adk had not been determined. To address this issue, we determined the crystal structure of the complex between Adk and the OPEN-form-specific monobody OP-4, employing hierarchical clustering analysis of X-ray diffraction datasets. The structure revealed that OP-4 binds to the surface formed by the expanded LID and CORE domains of Adk. Mutations in the interface residues reduced the OP- 4-binding affinity, indicating that the crystallographically identified interface is also relevant in solution. In particular, R123 mutations markedly impaired OP-4 binding. Molecular dynamics simulations further suggested that the R123-D159-R156 hydrogen-bond network is retained in solution and may contribute to efficient complex formation. These findings establish the structural basis for monobody OP-4 binding to open-form Adk and identify the R123-centered interaction network as a key determinant of complex formation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/742914v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@67570forg.highwire.dtl.DTLVardef@84b9caorg.highwire.dtl.DTLVardef@1c1b782org.highwire.dtl.DTLVardef@f6ed05_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe crystal structure of the OPEN-form adenylate kinase/monobody OP-4 complex was successfully determined. C_LIO_LIThe crystal structure revealed that OP-4 binds to surface formed by the expanded LID and CORE domains in adenylate kinase. C_LIO_LIIsothermal titration calorimetry measurements for adenylate kinase mutants confirmed that the binding modes observed in solution are consistent with those observed in the crystal structure. C_LIO_LIMolecular dynamics simulations suggested that the R123-D159-R156 hydrogen bond network prior to OP-4 binding is important for complex formation. C_LI

biochemistry↗

bioRxiv2022

High-resolution structure of a microtubule-like tube composed of FtsZ-monobody complexes

FtsZ, a bacterial tubulin homologue, forms protofilaments and the Z-ring, which acts as a scaffold for accessory proteins during cell division. Although various studies have revealed its molecular mechanisms, the lack of high-resolution solution structures has hindered the understanding of the detailed mechanisms. Here, we developed a monobody (Mb) that binds FtsZs from Escherichia coli and Klebsiella pneumoniae (KpFtsZ) without affecting their GTPase activities. When expressed in E. coli cells, the Mb did not inhibit Z-ring formation but did inhibit cell division. The crystal structures of the KpFtsZ-Mb complexes revealed the epitope, and the cryoEM structure at 2.67 [A] resolution showed a double helical tube consisting of two KpFtsZ protofilaments stabilized by the Mb filling interfilament gaps. Our structural analyses highlight the similarity between the microtubule and the FtsZ tube and the importance of the plasticity of FtsZ protofilaments.

molecular biology↗

bioRxiv2020

From Substance to Computation: Internalization and Hierarchical Structure in Evolutionary Phonology

In the history of phonological theory, the paradigm of computational systems has shifted in tandem with a better understanding of substantive issues such as typology, acquisition, social variation, and historical change in sound structure. The paradigm shift in the past 50 years can simply be characterized as the one from serial derivation by rules to parallel evaluation by constraints, and now Optimality Theory (OT) focusses on substantive issues by improving its phonetic groundings and has ceased groping for a better mode of computation. This is because OT is primarily a substantive theory of CON, and at least in its standard version, the computational systems of Eval and GEN are merely given assumptions. In this article, we will overview some arguments against OT in substantive respects. As an ultimate problem in substance, it cannot solve the poverty paradox, which means the paradox of the poverty of the stimulus in ontogeny and the poverty of the inheritance in phylogeny. Moreover, as a proximate problem in substance, certain gaps to be missed in syllable typology would erroneously be predicted to exist by OT. Alternatively, we will rethink the mode of computation in phonology and propose a new paradigm for phonology from the viewpoint of language evolution under a minimalist lens. Our proposal is based on Fujitas (2016a, 2017) Hypothesis on Motor Control Origin of Merge in Language Evolution, which solves the poverty paradox and thus satisfies both explanatory and evolutionary adequacy. We will demonstrate that substantive findings in OT can successfully be carried over to this scenario, in which the empirical problem concerning the typological gap is offered a reasonable explanation. We will also show that phonology has a vital role in computation and is not merely a subsidiary issue at the interface of the Sensory-Motor systems in linearization or externalization. We will take up one case for this claim: the English syllable CCVC has structural ambiguity, which means that phonology involves internalization with some mechanisms in order to create different hierarchical structures.

evolutionary biology↗