Genetic basis of the polymorphisms of the αI domain of spectrin

Abstract

Defects of alpha spectrin have been identified in many cases of hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP). To aid in the genetic analysis of families with these disorders, the locations of three alpha-spectrin gene polymorphisms were mapped, the genetic basis of these polymorphisms identified, and PCR-based assays designed for their identification. The frequencies of these polymorphisms were determined in two populations and in patients with alphaI/50a HE and HPP. These studies identified two distinct haplotypes and provided evidence that two HE/HPP mutations associated with the alphaI/50a protein phenotype, L207P and L260P, arose on separate chromosomal backgrounds.

Identification of the main ubiquitination site in human erythroid α‐spectrin

“…Spectrin heterodimers associate head‐to‐head to form tetramers, which in turn constitute the long, flexible filaments of the network. Spectrin also forms non‐covalent associations with other proteins of the erythrocyte skeleton, such as ankyrin, band 4.1 [13], actin, adducin and tropomyosin [14,15]. The α‐spectrin chain consists of 22 repeating segments, whereas the β‐spectrin chain consists of only 17 repeats.…”

“…The α‐spectrin chain consists of 22 repeating segments, whereas the β‐spectrin chain consists of only 17 repeats. The repeating segments of α‐spectrin, which are about 106 amino acids long, show sequence identity of about 20% but some residues are highly conserved, notably leucine and tryptophan at positions 26 and 45 of the repeats [13,15]. Recombinant DNA techniques have been used to produce fragments of spectrin that can serve as models for the native protein.…”

Spin label EPR structural studies of the N‐terminus of α‐spectrin

“…Members of the spectrin super‐family are found in many different cells. Human erythrocyte spectrin is responsible for cell flexibility and deformability [1], and is composed of two subunits, α‐spectrin (280 kDa) and β‐spectrin (246 kDa), which associate laterally to form heterodimers, which further associate to form the biologically significant tetramer [2,3]. Impaired tetramer formation leads to blood disorders [4,5].…”