8JHW

The first crystal structure of a H-2Kb-restricted decapeptide from Cryptosporidium parvum

Replaces:  8JHV

Summary for 8JHW

• Entry DOI: 10.2210/pdb8jhw/pdb
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, Beta-2-microglobulin, VAL-THR-PHE-GLU-LYS-SER-TYR-ASN-THR-VAL, ... (5 entities in total)
• Functional Keywords: cryptosporidium parvum; mhc i; t cell epitope; cell-mediated immunity, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 45005.56

Authors

Fan, S.,Wang, Y. (deposition date: 2023-05-25, release date: 2024-05-29, Last modification date: 2025-12-10)

Primary citation

Wang, Y.,Chang, Y.,Yin, F.,Kang, C.,Meng, Y.,Xu, F.,Liu, Y.,Zhang, Y.,Wu, C.,Fan, S.,Zhao, J.
Structural analyses of Cryptosporidium parvum epitopes reveal a novel scheme of decapeptide binding to H-2K b.
J.Struct.Biol., 217:108168-108168, 2025

PubMed Abstract: Cryptosporidium has gained much attention as a major cause of diarrhea worldwide. Here, we present the first structure of H-2K complexed with a decapeptide from Cryptosporidium parvum Gp40/15 protein (Gp40/15-VTF10). In contrast to all published structures, the aromatic residue P3-Phe of Gp40/15-VTF10 is anchored in pocket C rather than the canonical Y/F at P5 or P6 reported for octapeptides and nonapeptides. The results of in vitro refolding assays and circular dichroism experiments showed that the side chains of P3 and P5 play key roles in Gp40/15-VTF10 peptide binding. However, functional analysis of decapeptide epitopes revealed that the Gp40/15-VTF10 peptide did not elicit a strong CD8T immune response, whereas the decapeptide epitope MEDLE2-INF10 induced a significant CD8 T-cell response in peptide-immunized C57BL/6 mice. Using a model structure of H-2K-INF10 complex, we found that the antigenic decapeptide INF10 exhibits a completely different conformation, with the aromatic anchors P3F and P7F docked into the D and C pockets, respectively, while similar peptide conformation and hydrogen bond interactions between the peptide and major histocompatibility complex were found in the resolved H-2K-SVF9 complex. As the H-2K molecule predominantly prefers octapeptides with a strong anchor of P5 Y/F (or P6 Y/F for nonapeptides) binding to the C pocket, we propose that P7 Y/F in the C pocket may represent a novel binding mode for decapeptides. The results should increase the accuracy of T-cell epitope prediction and support the development of T-cell epitope vaccines against cryptosporidiosis.

PubMed: 39809366
DOI: 10.1016/j.jsb.2025.108168

Experimental method

X-RAY DIFFRACTION (3.12 Å)