A unique tetrameric structure of deer plasma haptoglobin – an evolutionary advantage in the Hp 2-2 phenotype with homogeneous structure

• Similar to blood types, human plasma haptoglobin (Hp) is classified intothree phenotypes: Hp 1-1, 2-1 and 2-2. They are genetically inheritedfrom two alleles Hp 1 and Hp 2 (represented in bold), but only theHp 1-1 phenotype is found in almost all animal species. The Hp 2-2protein consists of complicated large polymers cross-linked by a2-bsubunits or (a2-b)n (where n ‡ 3, up to 12 or more), and is associatedwith the risk of the development of diabetic, cardiovascular and inflammatorydiseases. In the present study, we found that deer plasma Hpmimics human Hp 2, containing a tandem repeat over the a-chain basedon our cloned cDNA sequence. Interestingly, the isolated deer Hp ishomogeneous and tetrameric, i.e. (a-b)4, although the locations of )SHgroups (responsible for the formation of polymers) are exactly identicalto that of human. Denaturation of deer Hp using 6 m urea under reducingconditions (143 mm b-mercaptoethanol), followed by renaturation,sustained the formation of (a-b)4, suggesting that the Hp tetramers arenot randomly assembled. Interestingly, an a-chain monoclonal antibody(W1), known to recognize both human and deer a-chains, only binds tointact human Hp polymers, but not to deer Hp tetramers. This impliesthat the epitope of the deer a-chain is no longer exposed on the surfacewhen Hp tetramers are formed. We propose that steric hindrance playsa major role in determining the polymeric formation in human and deerpolymers. Phylogenetic and immunochemical analyses revealed that theHp 2 allele of deer might have arisen at least 25 million years ago. Amechanism involved in forming Hp tetramers is proposed and discussed,and the possibility is raised that the evolved tetrameric structure of deerHp might confer a physiological advantage.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

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