Heme-ligand tunneling in group I truncated hemoglobins

Mario Milani, Alessandra Pesce, Yannick Ouellet, Sylvia Dewilde, Joel M. Friedman, Paolo Ascenzi, Michel Guertin, Martino Bolognesi

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Truncated hemoglobins (trHbs) are small hemoproteins forming a separate cluster within the hemoglobin superfamily; their functional roles in bacteria, plants, and unicellular eukaryotes are marginally understood. Crystallographic investigations have shown that the trHb fold (a two-on-two α-helical sandwich related to the globin fold) hosts a protein matrix tunnel system offering a potential path for ligand diffusion to the heme distal site. The tunnel topology is conserved in group I trHbs, although with modulation of its size/structure. Here, we present a crystallographic investigation on trHbs from Mycobacterium tuberculosis, Chlamydomonas eugametos, and Paramecium caudatum, showing that treatment of trHb crystals under xenon pressure leads to binding of xenon atoms at specific (conserved) sites along the protein matrix tunnel. The crystallographic results are in keeping with data from molecular dynamics simulations, where a dioxygen molecule is left free to diffuse within the protein matrix. Modulation of xenon binding over four main sites is related to the structural properties of the tunnel system in the three trHbs and may be connected to their functional roles. In a parallel crystallographic investigation on M. tuberculosis trHbN, we show that butyl isocyanide also binds within the apolar tunnel, in excellent agreement with concepts derived from the xenon binding experiments. These results, together with recent data on atypical CO rebinding kinetics to group I trHbs, underline the potential role of the tunnel system in supporting diffusion, but also accumulation in multiple copies, of low polarity ligands/molecules within group I trHbs.

Original languageEnglish (US)
Pages (from-to)21520-21525
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number20
DOIs
StatePublished - May 14 2004

Fingerprint

Truncated Hemoglobins
Heme
Tunnels
Xenon
Ligands
Mycobacterium tuberculosis
Paramecium caudatum
Modulation
Chlamydomonas
Proteins
Molecules
Globins
Molecular Dynamics Simulation
Carbon Monoxide
Eukaryota
Molecular dynamics
Structural properties
Bacteria
Hemoglobins
Topology

ASJC Scopus subject areas

  • Biochemistry

Cite this

Milani, M., Pesce, A., Ouellet, Y., Dewilde, S., Friedman, J. M., Ascenzi, P., ... Bolognesi, M. (2004). Heme-ligand tunneling in group I truncated hemoglobins. Journal of Biological Chemistry, 279(20), 21520-21525. https://doi.org/10.1074/jbc.M401320200

Heme-ligand tunneling in group I truncated hemoglobins. / Milani, Mario; Pesce, Alessandra; Ouellet, Yannick; Dewilde, Sylvia; Friedman, Joel M.; Ascenzi, Paolo; Guertin, Michel; Bolognesi, Martino.

In: Journal of Biological Chemistry, Vol. 279, No. 20, 14.05.2004, p. 21520-21525.

Research output: Contribution to journalArticle

Milani, M, Pesce, A, Ouellet, Y, Dewilde, S, Friedman, JM, Ascenzi, P, Guertin, M & Bolognesi, M 2004, 'Heme-ligand tunneling in group I truncated hemoglobins', Journal of Biological Chemistry, vol. 279, no. 20, pp. 21520-21525. https://doi.org/10.1074/jbc.M401320200
Milani M, Pesce A, Ouellet Y, Dewilde S, Friedman JM, Ascenzi P et al. Heme-ligand tunneling in group I truncated hemoglobins. Journal of Biological Chemistry. 2004 May 14;279(20):21520-21525. https://doi.org/10.1074/jbc.M401320200
Milani, Mario ; Pesce, Alessandra ; Ouellet, Yannick ; Dewilde, Sylvia ; Friedman, Joel M. ; Ascenzi, Paolo ; Guertin, Michel ; Bolognesi, Martino. / Heme-ligand tunneling in group I truncated hemoglobins. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 20. pp. 21520-21525.
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