Saeko Yanaka

Hydrogen-exchange behavior of the L20A mutant of the protein A B domain in guanidinium chloride: evidence for persistent native-like contacts

Seiichiro Hayashi, Saeko Yanaka, Maho Yagi‐Utsumi, Yukiko Isono et autres

Residual structure in unfolded proteins plays a crucial role in directing folding pathways. Here, we examined the unfolded state of the B domain of staphylococcal protein A carrying the L20A mutation, which disrupts native hydrophobic contacts between Leu20 and helix H3 (residues …

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Structural basis for the intestinal protocadherin-based intermicrovillar adhesion complex

Akinobu Senoo, Pablo Guillen-Poza, Karin Fujishima, Hirofumi Kosuge et autres

Abstract The intestinal brush border (BB), composed of densely packed microvilli on enterocytes, is essential for nutrient absorption and host defense. Its organization relies on the intermicrovillar adhesion complex (IMAC), mediated by protocadherins CDHR2 and CDHR5. Despite their clinical relevance in inflammatory …

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Characterization of high affinity IgM and IgG monoclonal antibodies against norovirus variants GII .4 and GII .17

Jumpei Tagawa, Saeko Yanaka, Yuri Kato, Akitsu Masuda et autres

Human noroviruses are a leading cause of acute gastroenteritis worldwide, yet the molecular principles governing antibody recognition of their highly repetitive capsid remain poorly understood. Here, we immunized mice with virus-like particles (VLPs) from the pandemic GII.4 strain and the emergent GII.17 …

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Stereochemical and Structural Characterization of Methionine Oxidation in the IgG1 Fc Region by Integrated NMR and LC-MS Analysis

Maho Yagi‐Utsumi, Saeko Yanaka, Noritaka Hashii, Kohei Tomita et autres

High Resolution Image Download MS PowerPoint Slide Monoclonal antibodies are widely used biotherapeutics, whose efficacy and pharmacokinetics critically depend on their structural integrity. Among chemical degradation pathways, methionine oxidation is a particularly important post-translational modification that compromises antibody stability, Fc receptor binding, …

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Unlabeled NMR Approach with Site-Specific Methyl Assignments for Structural Evaluation of the IgG1 Fc Region

Saeko Yanaka, Yuuki Koseki, Yohei Miyanoiri, Toshio Yamazaki et autres

Monoclonal antibodies are the cornerstone biopharmaceuticals whose safety and efficacy critically depend on their higher-order structure (HOS). Nuclear magnetic resonance (NMR) spectroscopy has emerged as a promising tool for HOS evaluation, yet its application has largely relied on fingerprinting approaches without residue-level …

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Key Role of Pro230 in the Hinge Region on the Architecture and Function of IgG1

Yuuki Koseki, Yuki Yamaguchi, Michihiko Aoyama, Kentaro Hiraka et autres

Immunoglobulin G (IgG) is a multifunctional glycoprotein essential for immune defense and widely used as a therapeutic due to its antigen specificity and effector functions. However, the inherent flexibility of its hinge region complicates structural characterization and obscures the molecular basis of …

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Methyl assignments of the Fc fragment of human IgG1 (fucosylated, non-galactosylated; FG0 glycoform)

Saeko Yanaka, Yuuki Koseki, Yohei Miyanoiri, Toshio Yamazaki et autres

Fc architecture and emerging principles in antibody engineering: From modular views to dynamic networks

Saeko Yanaka, Koichi Kato

Molecular mechanistic insights into the OX40 – OX40L complex from biophysical and computational analyses

Hiro Nishimuta, Akinobu Senoo, Keisuke Kasahara, Tai Kubo et autres

OX40 and OX40L belong to the tumor necrosis factor receptor superfamily (TNFRSF) and tumor necrosis factor superfamily (TNFSF), respectively. Protein-protein interactions between OX40 and OX40L facilitate T cell responses, triggering various immunological and pathophysiological events. Excessive activation frequently contributes to the onset …

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Structural basis for heme binding by the Shr protein from Streptococcus pyogenes

Akinobu Senoo, Satoru Nagatoishi, Saeko Yanaka, Makoto Nakakido et autres

Streptococcus pyogenes causes a range of infectious diseases. In an era of increasing antibiotic resistance, new antimicrobial strategies targeting virulence factors, rather than essential survival mechanisms, are being explored. A key virulence factor in S. pyogenes is the bacterial iron acquisition system, …

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Exploring glycoform-dependent dynamic modulations in human immunoglobulin G via computational and experimental approaches

Saeko Yanaka, Yoshitake Sakae, Yohei Miyanoiri, Takumi Yamaguchi et autres

We investigate the impact of glycoform alterations on the dynamic structure of the human immunoglobulin G1 (IgG1) Fc region using integrated computational and experimental approaches. Four distinct IgG1-Fc glycoforms, varying in core fucosylation and nonreducing terminal galactosylation, were generated through a combination …

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Temporal and Sex-Dependent N-Glycosylation Dynamics in Rat Serum

Hirokazu Yagi, Sachiko Kondo, Reiko Murakami, Rina Yogo et autres

We conducted systematic glycomic and glycoproteomic profiling to characterize the dynamic N-glycosylation landscape of rat serum, with particular focus on sex- and time-dependent variations. MALDI-TOF-MS analysis revealed that rat serum N-glycans are predominantly biantennary, disialylated complex-type structures with extensive O-acetylation of Neu5Ac …

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