5kd7

From Proteopedia
Jump to navigation Jump to search

Crystal Structure of Murine MHC-I H-2Dd in complex with Murine Beta2-Microglobulin and a Variant of Peptide (PV9) of HIV gp120 MN Isolate (IGPGRAFYV)Crystal Structure of Murine MHC-I H-2Dd in complex with Murine Beta2-Microglobulin and a Variant of Peptide (PV9) of HIV gp120 MN Isolate (IGPGRAFYV)

Structural highlights

5kd7 is a 12 chain structure with sequence from HIV-1 M:B_MN 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 2.35Å
Ligands:,
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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Frey BF, Jiang J, Sui Y, Boyd LF, Yu B, Tatsuno G, Billeskov R, Solaymani-Mohammadi S, Berman PW, Margulies DH, Berzofsky JA. Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity. J Immunol. 2018 Jan 26. pii: jimmunol.1701523. doi: 10.4049/jimmunol.1701523. PMID:29374075 doi:http://dx.doi.org/10.4049/jimmunol.1701523

5kd7, resolution 2.35Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA