Sanchez-Pulido Luis, Ponting Chris P
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
Bioinform Adv. 2022 Nov 24;2(1):vbac087. doi: 10.1093/bioadv/vbac087. eCollection 2022.
The 10 known BRICHOS domain-containing proteins in humans have been linked to an unusually long list of pathologies, including cancer, obesity and two amyloid-like diseases. BRICHOS domains themselves have been described as intramolecular chaperones that act to prevent amyloid-like aggregation of their proteins' mature polypeptides. Using structural comparison of coevolution-based AlphaFold models and sequence conservation, we identified the Out at First (OAF) protein as a new member of the BRICHOS family in humans. OAF is an experimentally uncharacterized protein that has been proposed as a candidate biomarker for clinical management of coronavirus disease 2019 infections. Our analysis revealed how structural comparison of AlphaFold models can discover remote homology relationships and lead to a better understanding of BRICHOS domain molecular mechanism.
Supplementary data are available at online.
人类已知的10种含BRICHOS结构域的蛋白质与一系列异常繁多的病症相关，包括癌症、肥胖症以及两种淀粉样疾病。BRICHOS结构域本身被描述为分子内伴侣，其作用是防止蛋白质成熟多肽发生淀粉样聚集。通过基于共进化的AlphaFold模型的结构比较和序列保守性分析，我们确定了“首次缺失”（OAF）蛋白是人类BRICHOS家族的新成员。OAF是一种未经实验表征的蛋白质，已被提议作为2019冠状病毒病感染临床管理的候选生物标志物。我们的分析揭示了AlphaFold模型的结构比较如何能够发现远缘同源关系，并有助于更好地理解BRICHOS结构域的分子机制。
补充数据可在 在线获取。
