人源胶原蛋白家族的结构域及进化分析  

Domain and Evolution Analysis of the Human Collagen Family

作　　者：潘成佳 吉丽娜[1] 华子春[1,2,3] PAN Chengjia;JI Lina;HUA Zichun(School of Life Sciences,Nanjing University,Nanjing 210023,China;Jiangsu Industrial Technology Research Institute,High-Tech Research Institute of Nanjing University,Changzhou 213164,China;Nanjing Jiruikang Biotechnology Research Institute,Nanjing 210046,China)

机构地区：[1]南京大学生命科学学院,医药生物技术全国重点实验室,江苏南京210023 [2]江苏省产业技术研究院医药生物技术研究所,常州南京大学高新技术研究院,江苏常州213164 [3]南京吉芮康生物科技研究院,江苏南京210046

出　　处：《药物生物技术》2024年第4期331-337,共7页Pharmaceutical Biotechnology

基　　金：江苏省自然科学基金(No.BK20230164、No.BK20230165、No.BK20231136);江苏省重点研发计划(No.BE2023695);常州市基础研究计划项目(No.2022169、No.CJ20235009、No.CJ20230017)。

摘　　要：胶原蛋白是一个复杂而庞大的家族,人胶原蛋白肽链的相对分子质量高达45~344 kD,共有44个家族成员。为了揭示人胶原蛋白的进化机制,本研究构建了人胶原蛋白的进化树,分析了其氨基酸序列中结构域和保守基序(motif)的种类及分布特点。结果发现人胶原蛋白具有14种结构域和10个motif,同一种结构域中往往包含相同的motif,进化树中同一分支上的胶原蛋白肽链也往往具有种类相同的结构域。在人胶原蛋白的非胶原结构域中,VWC结构域(von Willebrand factor type C domain)位于COL1A1、COL2A1、COL3A1和COL5A2中,这4种胶原蛋白位于人胶原蛋白全长序列进化树的同一分支上,但该分支中仅有COL1A2不包含VWC结构域。对不同物种COL1A2的N端序列进行多序列比对结果表明:COL1A2的VWC结构域在无脊椎动物向脊椎动物进化的过程中丢失。VWA结构域(von Willebrand factor type A domain)是胶原蛋白肽链中分布最广的非胶原结构域,存在于12种人胶原蛋白肽链中。VWA结构域蛋白质序列的BLAST比对结果表明,VWA结构域在人胶原蛋白的肽链之间复制。C4结构域(C-terminal tandem repeated domain intype 4 procollagen)只存在于IV型胶原蛋白中,对人胶原蛋白的C4结构域构建进化树,结果显示C4结构域中的C4-1和C4-2两个结构域进化速度一致,具有协同进化的现象。因此,胶原蛋白以结构域为基本进化单位,在进化中出现重复、缺失或协同进化的现象。Collagen,a complex and large family,spans a wide range of molecular weights.The molecular weight of human collagen chains can reach 45~344 kD,with a total of 44 family members.In order to reveal the evolutionary mechanism of human collagens,this study constructed an evolutionary tree of human full-length collagen sequences,analyzed the types and distribution patterns of domains and conserved motifs in their amino acid sequences.The result showed that human collagens have 14 different types of domains and 10 motifs.It was observed that domains of the same type often contains the same motifs,and collagen chains on the same branch of the evolutionary tree often have the same types of domains.In the non-collagenous domains of human collagens,the von Willebrand factor type C(VWC)domain exists in COL1A1,COL2A1,COL3A1,and COL5A2.These 4 types of collagens are located on the same branch of the human full-length collagen sequences evolutionary tree.However,only COL1A2 within this branch does not contain the VWC domain.Multiple sequence alignment of the N-terminal sequences of COL1A2 from different species indicates that the VWC domain of COL1A2 is lost during the evolution from invertebrates to vertebrates.Being present in 12 human collagen chains,the von Willebrand factor type A(VWA)domain is the most widely distributed non-collagenous domain in collagen chains.The BLAST analysis of VWA domain protein sequences reveals duplication of the VWA domain within peptide chains of human collagens.Conversely,the C-terminal tandem repeated domain in type 4 procollagen(C4)domain exists only in type IV collagen.An evolutionary tree was constructed based on the C4 domain of human collagens.The result shows that the evolutionary rates of the C4-1 and C4-2 domains within the C4 domain are consistent,indicating a phenomenon of co-evolution.In conclusion,the human collagen family evolves through domain-level mechanisms,with phenomena such as duplication,loss,and co-evolution throughout its evolutionary process.

关 键 词：胶原蛋白 进化分析 结构域 序列比对 保守基序 VWA结构域 VWC结构域 C4结构域 

分 类 号：Q512[生物学—生物化学]