标题: | A unique tetrameric structure of deer plasma haptoglobin - an evolutionary advantage in the Hp 2-2 phenotype with homogeneous structure |
作者: | Lai, I. H. Lin, Kung-Yu Larsson, Mikael Yang, Ming Chi Shiau, Chuen-Huei Liao, Ming-Huei Mao, Simon J. T. 生医工程研究所 Institute of Biomedical Engineering |
关键字: | amino acid sequence;deer and human haptoglobin;monoclonal antibody;phenotype;purification |
公开日期: | 1-三月-2008 |
摘要: | Similar to blood types, human plasma haptoglobin (Hp) is classified into three phenotypes: Hp 1-1, 2-1 and 2-2. They are genetically inherited from two alleles Hp 1 and Hp 2 (represented in bold), but only the Hp 1-1 phenotype is found in almost all animal species. The Hp 2-2 protein consists of complicated large polymers cross-linked by alpha 2-beta subunits or (alpha 2-beta)(n) (where n >= 3, up to 12 or more), and is associated with the risk of the development of diabetic, cardiovascular and inflammatory diseases. In the present study, we found that deer plasma Hp mimics human Hp 2, containing a tandem repeat over the alpha-chain based on our cloned cDNA sequence. Interestingly, the isolated deer Hp is homogeneous and tetrameric, i.e. (alpha-beta)(4), although the locations of -SH groups (responsible for the formation of polymers) are exactly identical to that of human. Denaturation of deer Hp using 6 M urea under reducing conditions (143 mM beta-mercaptoethanol), followed by renaturation, sustained the formation of (alpha-beta)(4), suggesting that the Hp tetramers are not randomly assembled. Interestingly, an alpha-chain monoclonal antibody (W1), known to recognize both human and deer alpha-chains, only binds to intact human Hp polymers, but not to deer Hp tetramers. This implies that the epitope of the deer alpha-chain is no longer exposed on the surface when Hp tetramers are formed. We propose that steric hindrance plays a major role in determining the polymeric formation in human and deer polymers. Phylogenetic and immunochemical analyses revealed that the Hp 2 allele of deer might have arisen at least 25 million years ago. A mechanism involved in forming Hp tetramers is proposed and discussed, and the possibility is raised that the evolved tetrameric structure of deer Hp might confer a physiological advantage. |
URI: | http://dx.doi.org/10.1111/j.1742-4658.2008.06267.x http://hdl.handle.net/11536/9626 |
ISSN: | 1742-464X |
DOI: | 10.1111/j.1742-4658.2008.06267.x |
期刊: | FEBS JOURNAL |
Volume: | 275 |
Issue: | 5 |
起始页: | 981 |
结束页: | 993 |
显示于类别: | Articles |
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