Govada Lata, Saridakis Emmanuel, Kassen Sean C, Bin-Ramzi Ahmad, Morgan Rhodri Marc, Chain Benjamin, Helliwell John R, Chayen Naomi E
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.
Structural and Supramolecular Chemistry Laboratory, Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research 'Demokritos', 15310 Athens, Greece.
IUCrJ. 2021 Jul 1;8(Pt 4):678-683. doi: 10.1107/S2052252521005340.
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.
C-C趋化因子受体5（CCR5）是HIV-1进入细胞所使用的主要共受体分子。这引发了一种假设，即刺激抗体反应可以以最小的毒性阻断HIV。在此，对抗CCR5抗体RoAb13与两种肽进行了X射线晶体学研究：一种肽是含有PIYDIN序列的31个残基的肽，另一种是单独的PIDYIN肽，其中PIYDIN是CCR5 N端区域的一部分，先前已证明该区域对HIV进入很重要。在较长肽（完整的N端结构域）存在的情况下，在高变CDR3结合区域内的一个位点观察到差异电子密度。在较短的核心肽PIYDIN存在的情况下，在这个CDR3位点再次观察到差异电子密度，证实了两种肽的一致结合。这可能有助于设计一种新的仿生制剂，以刺激针对CCR5的抗体反应，从而阻断HIV感染。
