Tang Wenjie, Zheng Kaixi, Sun Shengjie, Zhong Bo, Luo Zhan, Yang Junjie, Jia Lei, Yang Lan, Shang Wenna, Jiang Xiaofeng, Lyu Zhengbing, Chen Jianqing, Chen Guodong
School of Life Sciences, Central South University, Changsha 410031, China.
College of Life Sciences and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Int J Mol Sci. 2024 Nov 29;25(23):12879. doi: 10.3390/ijms252312879.
The variable domain of IgNAR shows great potential in biological medicine and therapy. IgNAR has been discovered in sharks and rays, with the nurse shark () IgNARs being the most extensively studied among sharks. Despite being identified in nurse sharks over 30 years ago, the characteristics and genomic localization of IgNAR remain poorly defined, with significant gaps even in the latest released genome data. In our research, we localized the IgNAR loci in the nurse shark genome and resolved the previously missing regions. We identified three IgNAR loci, designated , , and , with only and being expressed. GcIgNAR1 and GcIgNAR2 belong to type I and type II IgNARs, respectively, and each exhibits several different isoforms. Most nurse shark IgNARs possess five constant domains. However, we found transcripts of GcIgNAR1 and GcIgNAR2 lacking two constant domains, C4 and C5, which differ from the IgNAR of the whitespotted bamboo shark. The protein structures of GcIgNAR1 and GcIgNAR2, generated by AlphaFold3, confirmed the accuracy of the IgNAR loci we identified. Our findings advance scientific understanding of IgNAR in nurse sharks and facilitate future research and medical applications.
免疫球蛋白新抗原受体（IgNAR）的可变结构域在生物医药和治疗领域展现出巨大潜力。IgNAR在鲨鱼和鳐鱼中被发现，其中护士鲨的IgNAR是鲨鱼中研究最为广泛的。尽管30多年前就在护士鲨中被鉴定出来，但IgNAR的特征和基因组定位仍不清楚，即使在最新发布的基因组数据中也存在重大空白。在我们的研究中，我们在护士鲨基因组中定位了IgNAR基因座，并解析了之前缺失的区域。我们鉴定出三个IgNAR基因座，分别命名为、和，只有和表达。GcIgNAR1和GcIgNAR2分别属于I型和II型IgNAR，且各自呈现出几种不同的异构体。大多数护士鲨IgNAR具有五个恒定结构域。然而，我们发现GcIgNAR1和GcIgNAR2的转录本缺少两个恒定结构域C4和C5，这与点带竹鲨的IgNAR不同。由AlphaFold3生成的GcIgNAR1和GcIgNAR2的蛋白质结构证实了我们鉴定的IgNAR基因座的准确性。我们的发现推动了对护士鲨中IgNAR的科学理解，并促进了未来的研究和医学应用。
