X-ray crystallographic studies of RoAb13 bound to PIYDIN, a part of the N-terminal domain of C-C chemokine receptor 5

DOI: 10.1107/S2052252521005340

Authors: Lata Govada (Imperial College London) , Emmanuel Saridakis (National Centre for Scientific Research 'Demokritos') , Sean C. Kassen (Imperial College London) , Ahmad Bin-Ramzi (Imperial College London) , Rhodri Marc Morgan (Imperial College London) , Benjamin Chain (University College London) , John R. Helliwell (The University of Manchester) , Naomi E. Chayen (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Iucrj , VOL 8 , PAGES 678 - 683

State: Published (Approved)
Published: July 2021

Abstract: 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.

Journal Keywords: CCR5 receptor; RoAb13; HIV entry; PIYDIN; antibodies; structure determination; viruses; X-ray crystallography; structural biology

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-Macromolecular Crystallography

Added On: 02/07/2021 14:13

Documents:
mf5053.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)