5kd4

Crystal Structure of Murine MHC-I H-2Dd in complex with Murine Beta2-Microglobulin and a Variant of Peptide (PVI10) of HIV gp120 MN Isolate (IGPGRAFYVI)

spinqualitylabelsall models 5kd4, resolution 3.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kd4 is a 6 chain structure with sequence from Human immunodeficiency virus 1 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.05Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HA12_MOUSE Involved in the presentation of foreign antigens to the immune system. Publication Abstract from PubMed Unlike cytosolic processing and presentation of viral Ags by virus-infected cells, Ags first expressed in infected nonprofessional APCs, such as CD4(+) T cells in the case of HIV, are taken up by dendritic cells and cross-presented. This generally requires entry through the endocytic pathway, where endosomal proteases have first access for processing. Thus, understanding virus escape during cross-presentation requires an understanding of resistance to endosomal proteases, such as cathepsin S (CatS). We have modified HIV-1MN gp120 by mutating a key CatS cleavage site (Thr(322)Thr(323)) in the V3 loop of the immunodominant epitope IGPGRAFYTT to IGPGRAFYVV to prevent digestion. We found this mutation to facilitate cross-presentation and provide evidence from MHC binding and X-ray crystallographic structural studies that this results from preservation of the epitope rather than an increased epitope affinity for the MHC class I molecule. In contrast, when the protein is expressed by a vaccinia virus in the cytosol, the wild-type protein is immunogenic without this mutation. These proof-of-concept results show that a virus like HIV, infecting predominantly nonprofessional presenting cells, can escape T cell recognition by incorporating a CatS cleavage site that leads to destruction of an immunodominant epitope when the Ag undergoes endosomal cross-presentation. Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity.,Frey BF, Jiang J, Sui Y, Boyd LF, Yu B, Tatsuno G, Billeskov R, Solaymani-Mohammadi S, Berman PW, Margulies DH, Berzofsky JA J Immunol. 2018 Jan 26. pii: jimmunol.1701523. doi: 10.4049/jimmunol.1701523. PMID:29374075 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures

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