5kth

Structure of cow mincle complexed with brartemicin

spinqualitylabelsall models 5kth, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kth is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.21Å Ligands: 6X7, CA, GLC, PGE, PRD_900006 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E1BHM0_BOVIN Publication Abstract from PubMed The macrophage receptor mincle binds to trehalose dimycolate on the surface of Mycobacterium tuberculosis. Signaling initiated by this interaction leads to cytokine production, which underlies the ability of mycobacteria to evade the immune system and also to function as adjuvants. In previous work, the mechanism for binding of the sugar headgroup of trehalose dimycolate to mincle has been elucidated, but the basis for enhanced binding to glycolipid ligands, in which hydrophobic substituents are attached to the 6-hydroxyl groups, has been the subject of speculation. In the work reported here, the interaction of trehalose derivatives with bovine mincle has been probed with a series of synthetic mimics of trehalose dimycolate in binding assays, in structural studies by x-ray crystallography, and by site-directed mutagenesis. Binding studies reveal that, rather than reflecting specific structural preference, the apparent affinity of mincle for ligands with hydrophobic substituents correlates with their overall size. Structural and mutagenesis analysis provides evidence for interaction of the hydrophobic substituents with multiple different portions of the surface of mincle and confirms the presence of three Ca2+-binding sites. The structure of an extended portion of the extracellular domain of mincle, beyond the minimal C-type carbohydrate-recognition domain, also constrains the way that the binding domains may interact on the surface of macrophages. Binding sites for acylated trehalose analogs of glycolipid ligands on an extended carbohydrate-recognition domain of the macrophage receptor mincle.,Feinberg H, Rambaruth ND, Jegouzo SA, Jacobsen KM, Djurhuus R, Poulsen TB, Weis WI, Taylor ME, Drickamer K J Biol Chem. 2016 Aug 19. pii: jbc.M116.749515. PMID:27542410 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA