Conformational Changes in the Cytoplasmic Region of KIR3DL1 Upon Interaction with SHP-2
Copyright policy )Conformational Changes in the Cytoplasmic Region of KIR3DL1 Upon Interaction with SHP-2
KIR3DL1 is an inhibitory killer cell immunoglobulin-like receptor (KIR) that negatively regulates natural killer cell cytotoxicity. The KIR3DL1 cytoplasmic region (3DL1-cyto) is disordered and can be dissected into three segments: (I) H340-V351; (II) M352-D371; and (III) P372-P423. NMR studies indicate that segment II can dynamically adopt a loop-like conformation, and segments I and III can form dynamic helices that may mediate binding to membranes, particularly in the region around the N-terminal (N) immunoreceptor tyrosine-based inhibitory motif (ITIM), consistent with its role in signaling. Furthermore, individual SH2 domains of SHP-2 strongly engage with the unphosphorylated N-ITIM of 3DL1-cyto, while binding of the tandem SHP-2 SH2 domains to the bis-phosphorylated ITIMs results in more extensive conformational changes in segments I and III. The findings enhance our understanding of KIR function and how ITIMs in a target receptor operate in concert to engage the tandem SH2 domains of SHP-2.
- Fox Chase Cancer Center United States
- Temple University United States
Models, Molecular, Protein Conformation, alpha-Helical, Binding Sites, Sequence Homology, Amino Acid, Genetic Vectors, Gene Expression, Receptors, KIR3DL1, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Recombinant Proteins, Killer Cells, Natural, src Homology Domains, Kinetics, Escherichia coli, Humans, Amino Acid Sequence, Cloning, Molecular, Phosphorylation, Sequence Alignment, Protein Binding, Signal Transduction
Models, Molecular, Protein Conformation, alpha-Helical, Binding Sites, Sequence Homology, Amino Acid, Genetic Vectors, Gene Expression, Receptors, KIR3DL1, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Recombinant Proteins, Killer Cells, Natural, src Homology Domains, Kinetics, Escherichia coli, Humans, Amino Acid Sequence, Cloning, Molecular, Phosphorylation, Sequence Alignment, Protein Binding, Signal Transduction
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