5fb8

Structure of Interleukin-16 bound to the 14.1 antibody

spinqualitylabelsall models 5fb8, resolution 2.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fb8 is a 3 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, SO4, TRS Related: 1i16 Gene: IL16 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IL16_HUMAN] Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4. Isoform 1 may act as a scaffolding protein that anchors ion channels in the membrane. Isoform 3 is involved in cell cycle progression in T-cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells. Publication Abstract from PubMed Interleukin-16 (IL-16) is reported to be a chemoattractant cytokine and modulator of T-cell activation, and has been identified as a ligand for CD4. The secreted active form of IL-16 has been detected at sites of TH1-mediated inflammation, such as those seen in autoimmune diseases, ischemic reperfusion injury (IRI) and tissue transplant rejection. Neutralisation of IL-16 recruitment to CD4, using an anti-IL16 antibody, has been shown to significantly attenuate inflammation and disease pathology in IRI, as well as in some autoimmune diseases. The 14.1 antibody is a monoclonal anti-IL-16 antibody, which when incubated with CD4+ cells is reported to cause a reduction in the TH1-type inflammatory response. Secreted IL-16 contains a characteristic PDZ-domain. PDZ domains are typically characterised by a defined globular structure, along with a peptide-binding site located in a groove between the alphaB and betaB structural elements and a highly conserved carboxylate-binding loop. The structure of the 14.1Fab fragment in complex with IL-16 has been solved by X-ray crystallography, revealing that binding of the antibody requires a conformational change in the IL-16 PDZ-domain. Our study reveals an unexpected mechanism of action for the mAb and identifies new opportunities for the further development of IL-16 targeted therapeutic drugs, including small molecules that mimic the interaction of the antibody. Structure of a potential therapeutic antibody bound to IL-16: mechanistic insights and new therapeutic opportunities.,Hall G, Cullen E, Sawmynaden K, Arnold J, Fox S, Cowan R, Muskett FW, Matthews D, Merritt A, Kettleborough C, Cruikshank W, Taylor D, Bayliss R, Carr MD J Biol Chem. 2016 May 26. pii: jbc.M115.709303. PMID:27231345 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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