Smolarek D, Bertrand O, Czerwinski M, Colin Y, Etchebest C, de Brevern A G
Inserm UMR-S 665, dynamique des structures et interactions des macromolecules biologiques (DSIMB), 6, rue Alexandre-Cabanel, 75739 Paris cedex 15, France.
Transfus Clin Biol. 2010 Sep;17(3):184-96. doi: 10.1016/j.tracli.2010.05.003. Epub 2010 Jul 23.
Duffy Antigen Receptor for Chemokines (DARC) is an unusual transmembrane chemokine receptor which (i) binds the two main chemokine families and (ii) does not transduct any signal as it lacks the DRY consensus sequence. It is considered as silent chemokine receptor, a tank useful for chemiotactism. DARC had been particularly studied as a major actor of malaria infection by Plasmodium vivax. It is also implicated in multiple chemokine inflammation, inflammatory diseases, in cancer and might play a role in HIV infection and AIDS. In this review, we focus on the interest to build structural model of DARC to understand more precisely its abilities to bind its physiological ligand CXCL8 and its malaria ligand. We also present innovative development on VHHs able to bind DARC protein. We underline difficulties and limitations of such bioinformatics approaches and highlight the crucial importance of biological data to conduct these kinds of researches.
趋化因子的达菲抗原受体(DARC)是一种不同寻常的跨膜趋化因子受体,它(i)结合两个主要的趋化因子家族,并且(ii)由于缺乏DRY共有序列而不传导任何信号。它被认为是沉默趋化因子受体,是一种用于趋化作用的“容器”。DARC作为间日疟原虫疟疾感染的主要作用因子受到了特别研究。它还与多种趋化因子炎症、炎症性疾病、癌症有关,并且可能在HIV感染和艾滋病中发挥作用。在这篇综述中,我们聚焦于构建DARC结构模型以更精确地了解其结合生理配体CXCL8和疟疾配体能力的意义。我们还展示了能够结合DARC蛋白的VHHs的创新性进展。我们强调了此类生物信息学方法的困难和局限性,并突出了生物学数据对开展这类研究的至关重要性。