Haptoglobin (Hp) consists of light (L) and heavy (H) chains, the latter of which combine with hemoglobin αβ dimers to form a highly stable complex. Human haptoglobin assembles as HL units that occur in two allelic forms; HL 1, which is monovalent, and HL 2, which is divalent. As a result, three phenotypic forms exist in the human population: Hp1-1, the homozygous form in which the monovalent HL 1 unit occurs as a dimer; Hp2-2, the homozygous form of the divalent HL 2 unit, which gives a series of polymers; and the heterozygous Hp2-1 form, which gives a different series of polymers. We have investigated the structures and assembly properties of these two haptoglobin polymeric series in their complexes with hemoglobin using high-resolution scanning transmission electron microscopy. Polymers of complex are composed of ellipsoidal or bilobal head groups, which are the Hαβ subunits connected by thin filament-like structures, which are the L chains. Polymers of size up to pentamers can be identified easily by counting the number of head groups in the molecule. Complex 2-1 and complex 2-2 trimers were studied extensively. The differences in detailed morphology show that while the 2-1 trimer is a linear polymer, the 2-2 trimer is a closed circular molecule. The micrograph images suggest that complex 2-2 tetramers and pentamers, and perhaps higher forms may also be cyclic. The structure of the L 2 subunit of haptoglobin is shown to be composed of two domains, which may be similar in structure to the single domain of the monovalent L 1 chain. The two L 2 domains are connected by a hinge that has quite limited flexibility. Using these structural models, assembly characteristics and structural properties of the trimers and tetramers of complex 2-1 and complex 2-2 are described.
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