2017 Fiscal Year Annual Research Report
Thermodynamic basis of life: protein-carbohydrate interaction
| Project/Area Number |
15K06962
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| Research Institution | Kyushu University |
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Principal Investigator |
CAAVEIRO Jose 九州大学, 薬学研究院, 准教授 (00536732)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | glycan / sugar / antibody / enzyme / pore forming protein / X-ray crystallography / Thermodynamics / kinetics |
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| Outline of Annual Research Achievements |
1. Overall the project has surpassed the initial goals as I reason below, which leads me to affirm that this project has been a success. The scientific output until now comprises 15 papers and 11 presentations at international conferences and venues (invited, oral and posters), and it is very likely will increase as I publish more of the results obtained. This more than doubles the initial goal.
2. The project was also extended to study the effect of glycan in additional models systems, like antibodies and human protein OMD in collaboration with Professor Kouhei Tsumoto from The University of Tokyo.
3. The results show the importance of carbohydrates in a number of proteins, and dissect the energetic basis of their interaction. For example, we discovered that sugars can mimic lipids and recognize with low affinity a lipid-binding site. This could be an ancient mechanism of certain proteins to recognize a broad spectrum of cellular surfaces, since lipids and carbohydrates appear both on the external surface of cells.
4. In antibodies, the glycan moiety attached to the Fc region has a very subtle but key importance for the recognition of the cellular receptor Fcgamma. Although the sugar does not contact the receptor it influences the binding of the antibody to it. How? The glycan regulates the flexibility of the antibody, with longer glycans reducing the entropy of the protein, leading to stronger affinity.
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[Journal Article] Assessing the heterogeneity of the Fc-glycan of a therapeutic antibody using an engineered FcγReceptor IIIa-immobilized column2018
Author(s)
Kiyoshi, M., Caaveiro, J.M.M., Tada, M., Tamura, H., Tanaka, T., Terao, Y., Morante, K., Harazono, A., Hashii, N., Shibata, H., Kuroda, D., Nagatoishi, S., Oe, S., Ide, T., Tsumoto, K., and Ishii-Watabe, A.
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Journal Title
Sci. Rep.
Volume: 8
Pages: 3955
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody.2018
Author(s)
Miyanabe, K., Akiba, H., Kuroda, D., Nakakido, M., Kusano-Arai, O., Iwanari, H., Hamakubo, T., Caaveiro, J.M.M., and Tsumoto, K.
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Journal Title
J. Biochem.
Volume: in press
Pages: in press
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Weak electrostatic interactions between collagen and monomeric SLRP osteomodulin govern the shape of type I collagen fibrils2018
Author(s)
Tashima, T., Nagatoishi, S., Caaveiro, J.M.M., Nakakido, M., Sagara, H., Mimuro, H., Ohnuma, S-I., and Tsumoto, K.
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Journal Title
Commun. Biol.
Volume: 1
Pages: 33
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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