| Jose Caaveiro | Last modified date：2023.10.03 |
Professor /
Global Healthcare /
Faculty of Pharmaceutical Sciences
Reports
| 1. | Jose M.M. CAAVEIRO, Misaki ISHII, Makoto NAKAKIDO, and Kouhei TSUMOTO, Crystal structure of an antibody specific for methylated-lysine in complex with the cognate peptide, Photon Factory Activity Report , 2021.07, [URL], Methylation is an important posttranslational modification in proteins. We have prepared a number of methylysine- specific antibodies and characterized their mechanism of recognition. Herein we report the structure of the Fab region of the antibody termed D6 at a resolution of 1.8 Å. The mechanism of recognition involves a cage of three Trp residues surrounding the trimethylated portion of the modified lysine residue of the peptide.. |
| 2. | Jose M.M. Caaveiro, Kouhei Tsumoto, Molecular basis for the activation of actinoporins by lipids, Methods in Enzymology, https://doi.org/10.1016/bs.mie.2021.01.008, 2021.03, [URL], Actinoporins are a family of homologous pore forming proteins from sea anemones. They are one of the few families of eukaryotic toxins that have been characterized in depth. Actinoporins are activated by lipids in the context of bilayers, especially in cell and in model membranes containing the lipid sphingomyelin. These proteins must undergo conformational changes induced upon interaction with lipids in the membrane, where they form cytotoxic pores causing cell death and lethality. Herein we review a list of procedures and techniques to study this family of toxins, with the goal of elucidating the physicochemical, thermodynamic and structural basis for their activation by lipids. The emerging picture indicates that actinoporins undergo a stepwise process that includes binding to the membrane, oligomerization, and pore formation, in this order. The key transformation from the inactive oligomer to the active pore is catalyzed by sphingomyelin, explaining the key role of this lipid in the function of actinoporins.. |
| 3. | Recent virological researches using biophysical methods, termed as virus biophysics or virophysics, largely contribute to the development of anti-viral drugs and vaccines. In this review, examples of structural and physicochemical analyses for representative viruses to develop drug modalities such as small compounds, antibodies, and vaccines are explained, and future direction of biophysical research for virus research is also discussed., [URL]. |
| 4. | Jose M.M. Caaveiro, Hiroki Akiba, Hiroko Tamura, and Kouhei Tsumoto, Recognition of antigens by nanobodies from structural and energetic viewpoints., Photon Factory Activity Report, 2020.08, [URL], Single-domain antibodies (VHHs or nanobodies) from camelids are considered next-generation therapeutic biologicals. Although they display a small size, their affinity and specificity for antigens rival those of antibodies of the IgG class. The question that we aim to clarify in this study is how such small antibodies are able to reach such high performance.. |
| 5. | Caaveiro, J.M.M., Tashiro, S., and Tsumoto K., Structure-based discovery of new inhibitors of human DJ-1, a Parkinson’s disease related protein, Photon Factory Activity Report 36,243, 2019.07, [URL]. |
| 6. | Caaveiro, J.M.M., Morante, K., and Tsumoto K., Structure of the hemolytic toxin FraE helps to clarify the evolution of actinoporins., Photon Factory Activity Report, 36:242, 2019.07, [URL]. |
| 7. | Caaveiro, J.M.M., Kiyoshi, M., Ishii-Watabe, A., and Tsumoto K., Crystal structure of IgG-Fc bound to aglycosylated FcgammaRIIIa., Photon Factory Activity Report 35,100, 2018.08, [URL]. |
| 8. | Caaveiro, J.M.M., Miyanabe, K., and Tsumoto K., Intramolecular H-bonds facilitate the recognition of a flexible peptide by an antibody., Photon Factory Activity Report 35, 102, 2018.08, [URL]. |
| 9. | Caaveiro, J.M.M., Tashima, T., and Tsumoto K., Crystal structure of human osteomodulin., 2018.08, [URL]. |
| 10. | , [URL]. |
| 11. | , [URL]. |
| 12. | Kiyoshi, M., Tsumoto, K., Ishii-Watabe, A., Caaveiro, J.M.M., Glycosylation of IgG-Fc: a molecular perspective, Int. Immunol., 2017.09, [URL], ntibodies of the IgG class carry a pair of oligosaccharides (N-glycans) in the Fc region. The importance of the N-glycan is clearly demonstrated by the profound effect it has in the physicochemical and biological properties of antibodies. The term ‘glycoengineering’ has been coined to describe contemporary strategies to improve the performance of therapeutic monoclonal antibodies on the basis of modi cations in the structure and composition of the N-glycan. These methodologies have resulted in the approval and commercialization of a new generation of antibodies with improved therapeutic efficacy. So far, these advances have been driven by herculean efforts in a process of trial-and-error. The collective work of researchers in this eld is progressively revealing the molecular basis of N-glycans for the function of antibodies. This knowledge will ultimately be conducive to the application of rational approaches for the successful manipulation of antibodies using glycoengineering strategies. Herein, we review advances in our understanding of the role of the N-glycan in the structural and dynamic integrity, and biological activity, of antibodies. Since the N-glycan has a multifaceted effect in antibodies, in this review we have emphasized the importance of integrating various techniques that address this problem from multiple points of view. In particular, the combination of X-ray crystallography, with nuclear magnetic resonance, molecular dynamics simulations and biophysical approaches based on thermodynamic principles, has emerged as a powerful combination that is deepened our understanding of this unique system with critical implications for human well-being.. |
| 13. | Caaveiro, J.M.M., Tanaka, K., Tsumoto, K., Dual recognition of lipids and saccharides employing a single binding site in a pore forming toxin, Photon Factory Activity Report, 34, 98, 2017.07, [URL], Fragaceatoxin C (FraC) is a pore forming toxin (PFT) that interacts with biological membranes using a lipid binding motif. Since FraC also interact with the carbohydrates, we investigated the basis of glycan recognition. Surprisingly, we found that FraC engages glycans using the same, high-affinity, lipid-binding module. In conclusion, FraC has developed dual recognition capabilities with a single binding motif.. |
| 14. | Caaveiro, J.M.M., Rujas, E., Nieva, J.L., Tsumoto, K., Mechanism of recognition of a membrane-embedded epitope by the anti-HIV broadly-neutralizing 10E8 antibody., Photon Factory Activity Report, 34, 97, 2017.07, [URL], The mechanism by which the MPER epitope of gp41 of HIV-1 is recognized by the broadly neutralizing antibody 10E8 at membrane interfaces is not known. We determined the crystal structure of 10E8 Fab complex in complex with the transmembrane antigen in detergents. Our research clarifies the molecular mechanisms underlying broad neutralization by 10E8, and guiding future vaccination strategies targeting the MPER antigen of HIV-1.. |
| 15. | Tsumoto, K., Caaveiro, J.M.M., Antigen-Antibody Binding., Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester, 2016.12, [URL], Antibodies are a family of glycoproteins that bind specifically to target molecules (antigens). The antibody-binding sites are formed by six segments of variable structure (CDRs) supported by a scaffold of essentially invariant architecture (frame-work regions). Shape complementarity between the contact surfaces (in the case of protein antigens) or close interactions with small antigens (hapten, peptide or others), together with complementation of water molecules, are important to achieve high affinity and specificity. The binding of an antigen to an antibody takes place by the formation of multiple noncovalent bonds between the antigen and the amino acids of the binding site. The increase in van der Waals contacts and/or buried surfaces upon complexation generally correlates well with the binding strength. Hydrogen bonds are in most cases critical to achieve high specificity and affinity for the antigen target. Importantly, antibodies have at least two antigen binding sites, boosting the effective affinity of the antibody for its target by a mechanism termed avidity.. |
| 16. | Caaveiro, J.M.M., Kiyoshi, M., Ide, T., Tsumoto, K., Crystal structure of a human immune receptor in complex with the Fc region of the IgG antibody, PF Highlights 33, 48-49, 2016.09, [URL], Receptors of the Fc region of immunoglobulin-G (IgG) are key mediators of the immune response. In particular, human Fcgamma receptor I (hFcgammaRI) is the immune receptor with the highest affinity for IgG. To understand the molecular basis of interaction with antibodies, we determined the crystal structure of the complex between hFcgammaRI and human IgG-Fc at high resolution (1.80 Å). The structure reveals a deep and hydrophobic pocket explaining the strong affinity for IgG an- tibodies. We propose a general model for binding of IgG to Fc receptors on the cell surface. Our findings have implications for the development of novel therapeutic approaches involving hFcgammaRI.. |
| 17. | Morante, K., Caaveiro, J.M.M., Tsumoto, K., In-cell enzymology in heme oxygenase 1, Photon Factory Activity Report, 33, 191, 2016.07, [URL], Not available. |
| 18. | Kudo, S., Caaveiro, J.M.M., Tsumoto, K., Self-chaperoned dimerization of P-cadherin, Photon Factory Activity Report, 33, 190, 2016.07, [URL], Not available. |
| 19. | Rujas, E., Gulzar, N., Morante, K., Tsumoto, K., Scott, J.K., Nieva, J.L., Caaveiro, J.M.M., Reply to “The Broadly Neutralizing, Anti-HIV Antibody 4E10: an Open and Shut Case?”, J. Virol., 90, 3276-3277, 2016.02, [URL], Not available. |
| 20. | Caaveiro, J.M.M., Kiyoshi, M., Tsumoto, K., Structural Analysis of Fc/FcgammaR Complexes: A Blueprint for Antibody Design., Immunol. Rev., 268, 201-221, 2015.11, [URL], The number of studies and the quality of the structural data of Fcgamma receptors (FcgammaRs) has rapidly increased in the last few years. Upon critical examination of the literature, we have extracted general conclusions that could explain differences in affinity and selectivity of FcgammaRs for immunoglobulin G (IgG) based on structural considerations. FcgammaRs employ a little conserved asymmetric surface of domain D2 composed of two distinct subsites to recognize the well-conserved lower hinge region of IgG1-Fc. The extent of the contact interface with the antibody in subsite 1 of the receptor (but not in subsite 2), the geometrical complementarity between antibody and receptor, and the number of polar interactions contribute decisively toward strengthening the binding affinity of the antibody for the receptor. In addition, the uncertain role of the N-linked glycan of IgG for the binding and effector responses elicited by FccRs is discussed. The available data suggest that not only the non-covalent interactions between IgG and FccRs but also their dynamic features are essential for the immune response elicited through these receptors. We believe that the integration of structural, thermodynamic, and kinetic data will be critical for the design and validation of the next generation of therapeutic antibodies with enhanced effector capabilities.. |
| 21. | (Report in Japanese) Kudo, S., Caaveiro, J.M.M., Goda, S., Nagatoishi, S., Tsumoto, K., Identification of the ss-dimer and X-dimer of human P-cadherin by small angle X-ray scattering, Photon Factory Activity Report, 31, 086, [URL]. |
| 22. | (Report in Japanese) Tanaka, K., Morante, K., Caaveiro, J.M.M., Gonzalez-Manas, J.M., Tsumoto, K., Structural basis for activation of FraC, a toxin, Photon Factory Activity Report, 31, 85, [URL]. |
| 23. | (Report in Japanese) Tashiro, S., Caaveiro, J.M.M., Wu C.-X., Hoang, Q.Q., Tsumoto, K., Structural Characterization of the Specific Binding of Zn(II) to DJ-1, Photon Factory Activity Report, 31, 374, [URL]. |
| 24. | (Report in Japanese) Tanaka, K., Morante, K., Caaveiro, J.M.M., Gonzalez-Manas, J.M., Tsumoto, K. Metamorphosis of the pore-forming toxin FraC from the water-soluble to the transmembrane form, PF News 31(3), 17-20, [URL]. |
| 25. | Kobe, A., Kudo, S., Caaveiro, J.M.M., Tsumoto, K., Carbohydrate-protein interactions in the active site of sugar processing enzyme galactose mutarotase, Photon Factory Activity Report, 28, 267, 2011.07, [URL], Not available. |
| 26. | Miyafusa, T., Tanaka, Y., Caaveiro, J.M.M., Kuroda, M., Ohta, T., Tsumoto, K., Crystal structure of capsular polysaccharide synthesizing enzyme CapF, Photon Factory Activity Report, 28, 277, 2011.07, [URL], Not available. |
| 27. | Moriwaki, Y., Caaveiro, J.M.M., Tanaka, Y., Tsutsumi, H., Hamachi, I., Tsumoto, K., Molecular recognition of antibacterial porphyrins by IsdH-NEAT3, a protein involved in heme acquisition in pathogenic Staphylococcus aureus, Photon Factory Activity Report, 28, 266, 2011.07, [URL], Not available. |
| 28. | Nakakido, M., Caaveiro, J.M.M., Goda, S., Tsumoto, K., SAXS study of EbpS, a cell-wall associated protein of Staphylococcus aureus, Photon Factory Activity Report, 28, 270, 2011.07, [URL], Not available. |
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