[Structural biology of post-translational modifications of proteins].
A majority of proteins encoded in genomes of limited size are post-translationally diversified by covalent modifications such as glycosylation and ubiquitination. Although recent advances in structural proteomics have enabled high-throughput structure determination of proteins, structural analyses of post-translationally modified proteins remain challenging because of the lack of appropriate determination methods. Therefore, we developed methodologies for characterizing the post-translational modifications of proteins from the structural viewpoint, focusing especially on glycosylation and ubiquitination. For instance, we established a systematic method for structural glycomics to address broader issues, including glycosylation profiling and 3D structure analyses of glycoproteins. Our stable-isotope-assisted NMR techniques in conjunction with X-ray crystallographic approach provide valuable information at the atomic level on conformations, dynamics, and interactions of glycoproteins such as antibody and proteins involved in the ubiquitin-proteasome system. These studies provide the structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans and mechanistic insights into ubiquitination reactions in glycoprotein-fate determination in cells. These approaches will allow new possibilities for structural studies on post-translationally modified proteins of clinical, pathological, and pharmaceutical interests.
Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Aichi, Japan. kkato@phar.nagoya-cu.ac.jp
Koichi
K
Kato
D000906:Antibodies; D018360:Crystallography, X-Ray; D054794:Glycomics / Q000379:methods; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D057166:High-Throughput Screening Assays; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D040901:Proteomics; D054875:Ubiquitination
D000906:Antibodies; D006023:Glycoproteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011506:Proteins