Abstract

Haptoglobin (Hp) consists of light (L) and heavy (H) chains, the latter of which combine with hemoglobin alpha beta dimers to form a highly stable complex. Human haptoglobin assembles as HL units that occur in two allelic forms; HL1 , which is monovalent, and HL2 , which is divalent. As a result, three phenotypic forms exist in the human population: Hp1-1, the homozygous form in which the monovalent HL1 unit occurs as a dimer; Hp2-2, the homozygous form of the divalent HL2 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 H alpha beta 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 L2 subunit of haptoglobin is shown to be composed of two domains, which may be similar in structure to the single domain of the monovalent L1 chain. The two L2 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.

View details for Web of Science ID A1984SN18200006

View details for PubMedID 6716482