Figure 9: Suggestion of a cyclic peptide as a modulator of the CTLA-4/B7 interaction.
From: Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy
(a) Surface representations of the CTLA-4 molecule in the CTLA-4/B7-1 complex (left, PDB code 1i8l). The B7-1 binding site on the surface of CTLA-4 is coloured orange. Surface representations of CTLA-4 in the complex structures of CTLA-4/tremelimumab (right). The HCDR3 loop binding site on the surface of CTLA-4 is coloured blue. The overlapping region between the binding sites of B7-1 and HCDR3 is coloured red on the surface of CTLA-4 (centre). (b) Stereoview of the HCDR3 loop in the structure of CTLA-4/tremelimumab. The dashed line suggests a peptide bond between R101 and Y110 for generating a cyclic peptide. (c) Stereoview of a hypothetical model of the interaction between CTLA-4 (electrostatic surface representation) and the cyclic peptide based on the HCDR3 sequence of tremelimumab (yellow stick). The cyclic peptide was generated by connecting R101 and Y110 of the HCDR3 loop in the structure of CTLA-4/tremelimumab through a peptide bond, and its structure was polished by regularization and real space refinement in COOT (ref. 52). In this model, the cyclic peptide retains all of the interactions of HCDR3 in the structure of CTLA-4/tremelimumab.
