A wealth of genotype-specific proteoforms fine-tunes hemoglobin scavenging by haptoglobin.

ABSTRACT: The serum haptoglobin protein (Hp) scavenges toxic hemoglobin (Hb) leaked into the bloodstream from erythrocytes. In humans, there are two frequently occurring allelic forms of Hp, resulting in three genotypes: Homozygous Hp 1-1 and Hp 2-2, and heterozygous Hp 2-1. The Hp genetic polymorphism has an intriguing effect on the quaternary structure of Hp. The simplest form, Hp 1-1, forms dimers consisting of two α1β units, connected by disulfide bridges. Hp 2-1 forms mixtures of linear (α1)₂(α2)_n-2(β)_n oligomers (n > 1) while Hp 2-2 occurs in cyclic (α2)_n(β)_n oligomers (n > 2). Different Hp genotypes bind Hb with different affinities, with Hp 2-2 being the weakest binder. This behavior has a significant influence on Hp's anti

SUBMITTER: Tamara S 

PROVIDER: S-EPMC7355005 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature