X-ray crystallographic studies of RoAb13 bound to PIYDIN, a part of the N-terminal domain of C-C chemokine receptor 5.
X-ray crystallographic studies of RoAb13 bound to PIYDIN, a part of the N-terminal domain of C-C chemokine receptor 5.
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DOI：
10.1107/s2052252521005340
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发表时间：
2021-07-01
期刊：
影响因子：
3.9
通讯作者：
Chayen NE
中科院分区：
文献类型：
--
作者：
Govada L;Saridakis E;Kassen SC;Bin-Ramzi A;Morgan RM;Chain B;Helliwell JR;Chayen NE
C-C 趋化因子受体 5 (CCR5) 是 HIV-1 用来进入细胞的主要辅助受体分子。两项 X 射线晶体学研究显示了抗体 RoAb13，该抗体与肽 PIYDIN 结合，PIYDIN 是 CCR5 N 端结构域的一部分。这些结果可能为主动免疫疫苗提供基础，以刺激对天然 CCR5 的抗体反应，从而阻止 HIV 感染。 C-C 趋化因子受体 5 (CCR5) 是 HIV-1 用来进入细胞的主要辅助受体分子。这导致了这样的假设：刺激抗体反应可以以最小的毒性阻断艾滋病毒。在这里，对抗 CCR5 抗体 RoAb13 与两种肽一起进行了 X 射线晶体学研究：一种肽是包含 PIYDIN 序列的 31 个残基肽，另一种是单独的 PIDYIN 肽，其中 PIYDIN 是 CCR5 N 末端区域的一部分，之前已证明对 HIV 进入很重要。在存在较长肽（完整的 N 末端结构域）的情况下，在高变 CDR3 结合区内的位点观察到不同的电子密度。在存在较短核心肽 PIYDIN 的情况下，在此 CDR3 位点再次观察到不同的电子密度，证实了两种肽的结合一致。这可能有助于设计一种新的仿生剂，以刺激对 CCR5 的抗体反应，从而阻止 HIV 感染。
C-C chemokine receptor 5 (CCR5) is a major co-receptor molecule used by HIV-1 to enter cells. Two X-ray crystallographic studies are presented of the antibody RoAb13, which binds to the peptide PIYDIN, which is part of the N-terminal domain of CCR5. The results may provide the basis for active immunization vaccines to stimulate an antibody response to native CCR5 that will block HIV infection. 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.
影响因子：
5.5
作者：
Chain BM;Noursadeghi M;Gardener M;Tsang J;Wright E
通讯作者：
Wright E