The N-terminal 11 amino acids of human erythrocyte band 3 are critical for aldolase binding and protein phosphorylation: Implications for band 3 function

Silverio Perrotta, Adriana Borriello, Andrea Scaloni, Lucia De Franceschi, Anna Maria Brunati, Francesco Turrini, Vincenzo Nigro, Emanuele Miraglia Del Giudice, Bruno Nobili, Maria Luisa Conte, Francesca Rossi, Achille Iolascon, Arianna Donella-Deana, Vincenzo Zappia, Vincenzo Poggi, William Anong, Philip Low, Narla Mohandas, Fulvio Della Ragione

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The 911 amino acid band 3 (SLC4A1) is the major intrinsic membrane protein of red cells and is the principal Cl-/HCO3 - exchanger. The N-terminal cytoplasmic domain of band 3 anchors the spectrin-based membrane skeleton to the lipid bilayer through its interaction with ankyrin and also binds glycolytic enzymes and hemoglobin. We identified a son of a consanguineous marriage with severe anemia in association with marked deficiency of band 3 (12% ± 4% of normal). Direct nucleotide sequencing of SLC4A1 gene demonstrated a single base substitution (T→C) at position + 2 in the donor splice site of intron 2, resulting in the generation of a novel mutant protein. Biochemical characterization of the mutant protein showed that it lacked the first 11 N-terminal amino acids (band 3 Neapolis). The expression of the mutant protein resulted in the complete absence of membrane-bound aldolase, and the mutant band 3 could not be tyrosine phosphorylated. The ability of the malarial parasite P falciparum to invade these red cells was significantly decreased. The identification of a novel band 3 mutant and its structural and functional characterization enabled us to identify pivotal roles for the 11 N-terminal amino acids in several protein functions and, in turn, in red-cell physiology.

Original languageEnglish (US)
Pages (from-to)4359-4365
Number of pages7
JournalBlood
Volume106
Issue number13
DOIs
StatePublished - Dec 15 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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