Structural and functional studies of Hemoglobin Wayne: An elongated α-chain variant

Winston F. Moo-Penn, Danny L. Jue, Mary H. Johnson, Melisenda J. McDonald, Susan M. Turci, Tsu Bi Shih, Richard T. Jones, Bradford L. Therrell, Arthur Arnone

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Hemoglobin Wayne (Hb Wayne) is a frame-shift, elongated α-chain variant that exists in two forms, with either asparagine or aspartic acid as residue 139. Oxygen equilibrium studies showed that stripped Hb Wayne Asn and Hb Wayne Asp possessed high oxygen affinity (P 1 2 = 0.60 and 0.23 mmHg at pH 7, respectively), were non-co-operative and have a markedly reduced Bohr effect (-Δ log P 1 2/pH (7 to 8) = 0.34 and 0.10, respectively). Adding organic phosphate results in a decreased oxygen affinity and increased Bohr effect for both Hbs Wayne. The overall rate of carbon monoxide binding at pH 7 (l′ = 5.6 × 106 m-1 s-1) was similar for both stripped Hbs Wayne and was 25-fold more rapid than that of stripped Hb A. When organic phosphate was added, Hb Wayne Asn exhibited a homogeneous slower rate of carbon monoxide binding (l′ = 2.6 × 106 m-1 s-1), whereas Hb Wayne Asp showed heterogeneous binding (l′ = 6.1 × 106 and 2.6 × 106 m-1 s-1 for fast and slow phases, respectively). The rates of overall oxygen dissociation and oxygen dissociation with carbon monoxide replacement for both Hbs Wayne were found to be slow compared to Hb A and uniquely different from each other. Similarly, sedimentation velocity experiments indicated that, although Hb Wayne Asn and Hb Wayne Asp were both less tetrameric than Hb A, each hemoglobin exhibited a distinct degree of oxygen-linked subunit dissociation. These observed differences in the allosteric properties of Hb Wayne Asn and Hb Wayne Asp appeared to be directly attributable to residue 139. The equilibrium and kinetic data are consistent with the X-ray diffraction analysis of Hb Wayne Asp, which shows that the C terminus of the deoxytetramers are severely disordered, a condition that results in major destabilization of the T conformation and disruption of normal hemoglobin function.

Original languageEnglish (US)
Pages (from-to)1119-1140
Number of pages22
JournalJournal of Molecular Biology
Volume180
Issue number4
DOIs
StatePublished - Dec 25 1984
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Moo-Penn, W. F., Jue, D. L., Johnson, M. H., McDonald, M. J., Turci, S. M., Shih, T. B., Jones, R. T., Therrell, B. L., & Arnone, A. (1984). Structural and functional studies of Hemoglobin Wayne: An elongated α-chain variant. Journal of Molecular Biology, 180(4), 1119-1140. https://doi.org/10.1016/0022-2836(84)90273-0