X-ray crystallographic studies of RoAb13 bound to PIYDIN, a part of the N-terminal domain of C-C chemokine receptor 5
Lata Govada,
Emmanuel Saridakis,
Sean C. Kassen,
Ahmad Bin-Ramzi,
Rhodri Marc Morgan,
Benjamin Chain,
John R. Helliwell,
Naomi E. Chayen
Affiliations
Lata Govada
Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, United Kingdom
Emmanuel Saridakis
Structural and Supramolecular Chemistry Laboratory, Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research `Demokritos', 15310 Athens, Greece
Sean C. Kassen
Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, United Kingdom
Ahmad Bin-Ramzi
Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, United Kingdom
Rhodri Marc Morgan
Department of Life Sciences, Faculty of Natural Sciences, Sir Ernst Chain Building, Imperial College London, London SW7 2AZ, United Kingdom
Benjamin Chain
Division of Infection and Immunity, University College London, Gower Street, London, United Kingdom
John R. Helliwell
Department of Chemistry, The University of Manchester, Manchester M13 9PL, United Kingdom
Naomi E. Chayen
Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, United Kingdom
C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. This led to the hypothesis that stimulating an antibody response would block HIV with minimal toxicity. Here, X-ray crystallographic studies of the anti-CCR5 antibody RoAb13 together with two peptides were undertaken: one peptide is a 31-residue peptide containing the PIYDIN sequence and the other is the PIDYIN peptide alone, where PIYDIN is part of the N-terminal region of CCR5 previously shown to be important for HIV entry. In the presence of the longer peptide (the complete N-terminal domain), difference electron density was observed at a site within a hypervariable CDR3 binding region. In the presence of the shorter core peptide PIYDIN, difference electron density is again observed at this CDR3 site, confirming consistent binding for both peptides. This may be useful in the design of a new biomimetic to stimulate an antibody response to CCR5 in order to block HIV infection.
