7nwz

ALK:ALKAL2 complex

spinqualitylabelsall models 7nwz, resolution 4.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nwz is a 6 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 4.17Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALKL2_HUMAN Ligand for receptor tyrosine kinases LTK and ALK. Stimulation of ALK signaling may be involved in regulation of cell proliferation and transformation. Publication Abstract from PubMed Anaplastic lymphoma kinase (ALK)(1) and the related leukocyte tyrosine kinase (LTK)(2) are recently deorphanized receptor tyrosine kinases(3). Together with their activating cytokines, ALKAL1 and ALKAL2(4-6) (also called FAM150A and FAM150B or AUGbeta and AUGalpha, respectively), they are involved in neural development(7), cancer(7-9) and autoimmune diseases(10). Furthermore, mammalian ALK recently emerged as a key regulator of energy expenditure and weight gain(11), consistent with a metabolic role for Drosophila ALK(12). Despite such functional pleiotropy and growing therapeutic relevance(13,14), structural insights into ALK and LTK and their complexes with cognate cytokines have remained scarce. Here we show that the cytokine-binding segments of human ALK and LTK comprise a novel architectural chimera of a permuted TNF-like module that braces a glycine-rich subdomain featuring a hexagonal lattice of long polyglycine type II helices. The cognate cytokines ALKAL1 and ALKAL2 are monomeric three-helix bundles, yet their binding to ALK and LTK elicits similar dimeric assemblies with two-fold symmetry, that tent a single cytokine molecule proximal to the cell membrane. We show that the membrane-proximal EGF-like domain dictates the apparent cytokine preference of ALK. Assisted by these diverse structure-function findings, we propose a structural and mechanistic blueprint for complexes of ALK family receptors, and thereby extend the repertoire of ligand-mediated dimerization mechanisms adopted by receptor tyrosine kinases. Structural basis of cytokine-mediated activation of ALK family receptors.,De Munck S, Provost M, Kurikawa M, Omori I, Mukohyama J, Felix J, Bloch Y, Abdel-Wahab O, Bazan JF, Yoshimi A, Savvides SN Nature. 2021 Oct 13. pii: 10.1038/s41586-021-03959-5. doi:, 10.1038/s41586-021-03959-5. PMID:34646012 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine kinase receptor 3D structures

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