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Start Over Author "Saeko Yanaka" Journal journal of biological chemistry
2 results on '"Saeko Yanaka"'

1. Non-core Region Modulates Interleukin-11 Signaling Activity

Author

Saeko Yanaka, Emiko Sano, Norio Naruse, Kin-ichiro Miura, Mutsumi Futatsumori-Sugai, Jose M.M. Caaveiro, and Kouhei Tsumoto

Subjects
Agonist, endocrine system, Glycosylation, medicine.drug_class, medicine.medical_treatment, Interleukin, Biological activity, Cell Biology, Biology, Glycoprotein 130, Biochemistry, Cell biology, Interleukin 11, chemistry.chemical_compound, Cytokine, chemistry, medicine, Signal transduction, Molecular Biology
Abstract

Human interleukin-11 (hIL-11) is a pleiotropic cytokine administered to patients with low platelet counts. From a structural point of view hIL-11 belongs to the long-helix cytokine superfamily, which is characterized by a conserved core motif consisting of four α-helices. We have investigated the region of hIL-11 that does not belong to the α-helical bundle motif, and that for the purpose of brevity we have termed "non-core region." The primary sequence of the interleukin was altered at various locations within the non-core region by introducing glycosylation sites. Functional consequences of these modifications were examined in cell-based as well as biophysical assays. Overall, the data indicated that the non-core region modulates the function of hIL-11 in two ways. First, the majority of muteins displayed enhanced cell-stimulatory properties (superagonist behavior) in a glycosylation-dependent manner, suggesting that the non-core region is biologically designed to limit the full potential of hIL-11. Second, specific modification of a predicted mini α-helix led to cytokine inactivation, demonstrating that this putative structural element belongs to site III engaging a second copy of cell-receptor gp130. These findings have unveiled new and unexpected elements modulating the biological activity of hIL-11, which may be exploited to develop more versatile medications based on this important cytokine.

Published
2011
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2. Peptide-dependent Conformational Fluctuation Determines the Stability of the Human Leukocyte Antigen Class I Complex.

Author

Saeko Yanaka, Takamasa Ueno, Yi Shi, Jianxun Qi, Gao, George F., Kouhei Tsumoto, and Kenji Sugase

Subjects
*HLA histocompatibility antigen genetics, *IMMUNOGENETICS, *T cell receptors, *HUMAN T cell receptors, *T cells, *CANCER
Abstract

In immune-mediated control of pathogens, human leukocyte antigen (HLA) class I presents various antigenic peptides to CD8+ T-cells. Long-lived peptide presentation is important for efficient antigen-specific T-cell activation. Presentation time depends on the peptide sequence and the stability of the peptide- HLA complex (pHLA). However, the determinant of peptide- dependent pHLA stability remains elusive. Here, to reveal the pHLA stabilization mechanism, we examined the crystal structures of an HLA class I allomorph in complex with HIVderived peptides and evaluated site-specific conformational fluctuations using NMR. Although the crystal structures of various pHLAs were almost identical independent of the peptides, fluctuation analyses identified a peptide-dependent minor state that would be more tightly packed toward the peptide. The minor population correlated well with the thermostability and cell surface presentation of pHLA, indicating that this newly identified minor state is important for stabilizing the pHLA and facilitating T-cell recognition. [ABSTRACT FROM AUTHOR]

Published
2014
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