The first structure of a protein from the SOUL/HBP family of heme-binding proteins: Murine p22HBP

Jorge da Silva Dias, Maria dos Anjos López de Macedo, Glória C. Ferreira, Francis C. Peterson, Brian F. Volkman, Brian J. Goodfellow

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Murine p22HBP, a 22-kDa monomer originally identified as a cytosolic heme-binding protein ubiquitously expressed in various tissues, has 27% sequence identity to murine SOUL, a heme-binding hexamer specifically expressed in the retina. In contrast to murine SOUL, which binds one heme per subunit via coordination of the Fe(III)-heme to a histidine, murine p22HBP binds one heme molecule per subunit with no specific axial ligand coordination of the Fe(III)-heme. Using intrinsic protein fluorescence quenching, the values for the dissociation constants of p22HBP for hemin and protoporphyrin-IX were determined to be in the low nanomolar range. The three-dimensional structure of murine p22HBP, the first for a protein from the SOUL/HBP family, was determined by NMR methods to consist of a 9-stranded distorted β-barrel flanked by two long α-helices. Although homologous domains have been found in three bacterial proteins, two of which are transcription factors, the fold determined for p22HBP corresponds to a novel α plus β fold in a eukaryotic protein. Chemical shift mapping localized the tetrapyrrole binding site to a hydrophobic cleft formed by residues from helix αA and an extended loop. In an attempt to assess the structural basis for tetrapyrrole binding in the SOUL/HBP family, models for the p22HBP-protoporphyrin-IX complex and the SOUL protein were generated by manual docking and automated methods.
Original languageEnglish
Pages (from-to)31553-31561
Number of pages9
JournalThe Journal of biological chemistry
Volume281
Issue numberNA
DOIs
Publication statusPublished - 20 Oct 2006

Keywords

  • Protein fluorescence quenching
  • Retina
  • Ligands
  • Protoporphyrin

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