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A unique tetrameric structure of deer plasma haptoglobin – an evolutionary advantage in the Hp 2‐2 phenotype with homogeneous structure
Author(s) -
Lai I. H.,
Lin KungYu,
Larsson Mikael,
Yang Ming Chi,
Shiau ChuenHuei,
Liao MingHuei,
Mao Simon J. T.
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06267.x
Subject(s) - haptoglobin , phenotype , antibody , epitope , chemistry , alpha chain , alpha (finance) , beta (programming language) , homogeneous , microbiology and biotechnology , biology , biochemistry , genetics , gene , immunology , medicine , construct validity , nursing , physics , patient satisfaction , computer science , programming language , thermodynamics
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 α2‐β subunits or (α2‐β) 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 α‐chain based on our cloned cDNA sequence. Interestingly, the isolated deer Hp is homogeneous and tetrameric, i.e. (α‐β) 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 m m β‐mercaptoethanol), followed by renaturation, sustained the formation of (α‐β) 4 , suggesting that the Hp tetramers are not randomly assembled. Interestingly, an α‐chain monoclonal antibody (W1), known to recognize both human and deer α‐chains, only binds to intact human Hp polymers, but not to deer Hp tetramers. This implies that the epitope of the deer α‐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.