3BGM

Crystal Structure of PKD2 Phosphopeptide Bound to Human Class I MHC HLA-A2

Summary for 3BGM

• Entry DOI: 10.2210/pdb3bgm/pdb
• Related: 3BH8 3BH9 3BHA 3BHB
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, nonameric peptide from Serine/threonine-protein kinase D2, ... (5 entities in total)
• Functional Keywords: phosphoserine, phosphopeptide, mhc, hla-a2, anchor residue, tumor antigen, glycoprotein, host-virus interaction, immune response, mhc i, polymorphism, transmembrane, ubl conjugation, immunoglobulin domain, kinase, phosphoprotein, serine/threonine-protein kinase, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769; Cytoplasm (By similarity): Q9BZL6
• Total number of polymer chains: 3
• Total formula weight: 44893.79

Authors

Mohammed, F.,Cobbold, M.,Zarling, A.L.,Salim, M.,Barrett-Wilt, G.A.,Shabanowitz, J.,Hunt, D.F.,Engelhard, V.H.,Willcox, B.E. (deposition date: 2007-11-27, release date: 2008-10-21, Last modification date: 2024-10-30)

Primary citation

Mohammed, F.,Cobbold, M.,Zarling, A.L.,Salim, M.,Barrett-Wilt, G.A.,Shabanowitz, J.,Hunt, D.F.,Engelhard, V.H.,Willcox, B.E.
Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self
Nat.Immunol., 9:1236-1243, 2008

PubMed Abstract: Protein phosphorylation generates a source of phosphopeptides that are presented by major histocompatibility complex class I molecules and recognized by T cells. As deregulated phosphorylation is a hallmark of malignant transformation, the differential display of phosphopeptides on cancer cells provides an immunological signature of 'transformed self'. Here we demonstrate that phosphorylation can considerably increase peptide binding affinity for HLA-A2. To understand this, we solved crystal structures of four phosphopeptide-HLA-A2 complexes. These identified a novel peptide-binding motif centered on a solvent-exposed phosphate anchor. Our findings indicate that deregulated phosphorylation can create neoantigens by promoting binding to major histocompatibility complex molecules or by affecting the antigenic identity of presented epitopes. These results highlight the potential of phosphopeptides as novel targets for cancer immunotherapy.

PubMed: 18836451
DOI: 10.1038/ni.1660

Experimental method

X-RAY DIFFRACTION (1.6 Å)