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A Phylogenetic and Structural Analysis of Truncated Hemoglobins

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Abstract

Truncated hemoglobins (trHbs) are heme proteins found in bacteria, plants, and unicellular eukaryotes. They are distantly related to vertebrate hemoglobins and are typically shorter than these by 20–40 residues. The multiple amino acid deletions, insertions, and replacements result in distinctive alterations of the canonical globin fold and a wide range of chemical properties. An early phylogenetic analysis categorized trHbs into three groups, I (trHbN), II (trHbO), and III (trHbP). Here, we revisit this analysis with 111 trHbs. We find that trHbs are orthologous within each group and paralogous across the groups. Group I globins form the most disparate set and separate into two divergent subgroups. Group II is comparatively homogeneous, whereas Group III displays the highest level of overall conservation. In Group I and Group II globins, for which some ligand binding and structural data are available, an improved description of probable protein-ligand interactions is achieved. Other conservation trends are either confirmed (essential glycines in loops), refined (lining of ligand access tunnel), or newly identified (helix start signal). The Group III globins, so far uncharacterized, exhibit recognizable heme cavity residues while lacking some of the residues thought to be important to the trHb fold. An analysis of the phylogenetic trees of each group provides a plausible scenario for the emergence of trHbs, by which the Group II trHb gene was the original gene, and the Group I trHb and Group III trHb genes were obtained via duplication and transfer events.

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Notes

  1. By convention, trHbs are aligned with Physeter catodon (sperm whale) myoglobin and discussed using the customary helix numbering (Perutz 1979).

  2. Tyr B10, which is strictly conserved, is engaged in a covalent bond through its Oη atom with Tyr CD1 in a portion of the crystallized molecules, presumably increasing the stability of the bound state (Milani et al. 2003). It is not known whether this posttranslational modification occurs in vivo.

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Acknowledgments

This work was supported by NSF Grant MCB-0349409 and NASA Grant NNG04GN33H (D.A.V.). We thank Dr. Arthur Lesk and Nancy Scott for useful discussions and Drs. Don Bryant and Michel Guertin for their careful reading of the manuscript and many suggestions.

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  1. Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park,, PA, 16802, USA

    David A. Vuletich & Juliette T.J. Lecomte

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  1. David A. Vuletich
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  2. Juliette T.J. Lecomte
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Correspondence to Juliette T.J. Lecomte.

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Vuletich, D.A., Lecomte, J.T. A Phylogenetic and Structural Analysis of Truncated Hemoglobins. J Mol Evol 62, 196–210 (2006). https://doi.org/10.1007/s00239-005-0077-4

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