Syntaxin binding mechanism and disease-causing mutations in Munc18-2
Copyright policy )Syntaxin binding mechanism and disease-causing mutations in Munc18-2
Significance Understanding the molecular mechanisms that control secretion from cytotoxic T lymphocytes (CTL) and natural killer (NK) cells is the key for understanding how these cells destroy virally infected and tumourigenic cells. Precisely how mutations in Munc18-2 and syntaxin 11 (Stx11) give rise to loss of CTL and NK function and severe immunodeficiency is poorly understood. In this study we present a crystal structure of human Munc18-2 and analyze the disease-causing mutations. Our findings reveal a mechanism that allows Munc18-2 to selectively bind Stx11 and identify potential surrogate binding partners, which could restore Munc18-Stx function upon IL-2 activation.
- University of Cambridge United Kingdom
- University of Freiburg Germany
- University of Cologne Germany
- Universität Hamburg Germany
- University Medical Center Hamburg-Eppendorf Germany
Models, Molecular, Qa-SNARE Proteins, Blotting, Western, Spodoptera, Immunohistochemistry, Lymphohistiocytosis, Hemophagocytic, Evolution, Molecular, Killer Cells, Natural, HEK293 Cells, Munc18 Proteins, Sf9 Cells, Animals, Humans, Point Mutation, Crystallization, Protein Binding, T-Lymphocytes, Cytotoxic
Models, Molecular, Qa-SNARE Proteins, Blotting, Western, Spodoptera, Immunohistochemistry, Lymphohistiocytosis, Hemophagocytic, Evolution, Molecular, Killer Cells, Natural, HEK293 Cells, Munc18 Proteins, Sf9 Cells, Animals, Humans, Point Mutation, Crystallization, Protein Binding, T-Lymphocytes, Cytotoxic
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