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Journal Articles Biochimica et Biophysica Acta Proteins and Proteomics Year : 2013

Primary processes in heme-based sensor proteins

Ursula Liebl
Marten H. Vos


A wide and still rapidly increasing range of heme-based sensor proteins has been discovered over the last two decades. At the molecular level, these proteins function as bistable switches in which the catalytic activity of an enzymatic domain is altered mostly by binding or dissociation of small gaseous ligands (O2, NO or CO) to the heme in a sensor domain. The initial "signal" at the heme level is subsequently transmitted within the protein to the catalytic site, ultimately leading to adapted expression levels of specific proteins. Making use of the photolability of the heme-ligand bond that mimics thermal dissociation, early processes in this intra-protein signaling pathway can be followed using ultrafast optical spectroscopic techniques; they also occur on timescales accessible to molecular dynamics simulations. Experimental studies performed over the last decade on proteins including the sensors FixL (O2), CooA (CO) and soluble guanylate cyclase (NO) are reviewed with an emphasis on emerging general mechanisms. After heme-ligand bond breaking, the ligand can escape from the heme pocket and eventually from the protein, or rebind directly to the heme. Remarkably, in all sensor proteins the rebinding, specifically of the sensed ligand, is highly efficient. This "ligand trap" property possibly provides means to smoothen the effects of fast environmental fluctuations on the switching frequency. For 6-coordinate proteins, where exchange between an internal heme-bound residue and external gaseous ligands occurs, the study of early processes starting from the unliganded form indicates that mobility of the internal ligand may facilitate signal transfer. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. Cop. 2013 Elsevier B.V. All rights reserved.

Dates and versions

hal-00817153 , version 1 (06-05-2013)



Ursula Liebl, Jean-Christophe Lambry, Marten H. Vos. Primary processes in heme-based sensor proteins. Biochimica et Biophysica Acta Proteins and Proteomics, 2013, 1834 (9), pp.1684-1692. ⟨10.1016/j.bbapap.2013.02.025⟩. ⟨hal-00817153⟩
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