3qs7 | pdb_00003qs7

Crystal structure of a human Flt3 ligand-receptor ternary complex

spinqualitylabelsall models 3qs7, resolution 4.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qs7 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 4.3Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FLT3L_HUMAN Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins. Publication Abstract from PubMed The class-III receptor tyrosine kinase (RTKIII) Flt3 and its cytokine ligand (FL) play central roles in hematopoiesis and the immune system, by establishing signaling cascades crucial for the development and homeostasis of hematopoietic progenitors and antigen-presenting dendritic cells. However, Flt3 is also one of the most frequently mutated receptors in hematological malignancies and is currently a major prognostic factor and clinical target for acute myeloid leukemia (AML). Here, we report the structural basis for the Flt3 ligand-receptor complex and unveil an unanticipated extracellular assembly unlike any other RTKIII/V complex characterized to date. FL induces dimerization of Flt3 via a remarkably compact binding epitope localized at the tip of extracellular domain 3 of Flt3, and invokes a ternary complex devoid of homotypic receptor interactions. Comparisons of Flt3 with homologous receptors and available mutagenesis data for FL have allowed us to rationalize the unique features of the Flt3 extracellular assembly. Furthermore, thermodynamic dissection of complex formation points to a pronounced enthalpically-driven binding event coupled to an entropic penalty. Together, our data suggest that the high-affinity Flt3-FL complex is driven in part by a single preformed binding epitope on FL reminiscent of a 'lock-and-key' binding mode, thereby setting the stage for antagonist design. Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex.,Verstraete K, Vandriessche G, Januar M, Elegheert J, Shkumatov AV, Desfosses A, Van Craenenbroeck K, Svergun DI, Gutsche I, Vergauwen B, Savvides SN Blood. 2011 Mar 9. PMID:21389326 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine kinase 3D structures

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