Variations on the theme: allosteric control in hemoglobin

Abstract

Conformational selection between pre‐existing structural states of an oligomeric protein was the conceptual step behind the formulation of Monod–Wyman–Changeux (MWC) allosteric theory. Variations on the basic theme of allosteric control are briefly illustrated in this paper by reference to some hemoglobins from different species whose functional properties were found to respond to specific physiological requirements. In my opinion the enormous success of the allosteric theory may be attributed not only to its efficiency in accounting for data and its formal mathematical elegance, but also because the selective mechanism conforms to the founding concept of Darwinian evolution.

Interspecific Differences in the Metabolic Rate, Gill Dimension and Hematology of Fish in an Amazonian Floodplain Lake

“…In general, more than 90% of the oxygen transported from the gill epithelium is carried by hemoglobin (Nikinmaa & Soivio 2005). The number of circulating red blood cells, the hemoglobin concentration, the amount of oxygen-binding hemoglobin (modulated by the erythrocyte environment) and the properties of the prevailing oxygen partial pressure all determine the amount of oxygen carried per unit volume of blood (Brunori 2014). Unfortunately, neither the kinetic properties of hemoglobin nor the blood oxygen content were analyzed in this study, but the circulating red cell blood and total hemoglobin content favors species-specific adjustments to carry oxygen, depending on the metabolic demand of each animal.…”

“…In contrast, fish that live in benthic environments have large cell volumes. It is possible that cell volume may influence hemoglobin-oxygen affinity (Brunori 2014). As the bottom environment in floodplain lakes is usually hypoxic or anoxic (Anjos et al 2008), it is possible that a higher cell volume may be advantageous for benthic fish.…”

“…If the gill structures are matched to oxygen uptake in water, it is expected that blood oxygen carrying capacity is also adjusted to metabolic rate. The oxygen transport in the blood may depend directly on (i) the number of circulating red blood cells and hemoglobin concentration and (ii) the functional properties of hemoglobin and its allosteric modulators (Nikinmaa & Soivio 2005;Brunori 2014). It has been reported that active swimming fish have more circulating red cell blood and high hemoglobin levels, while sluggish fish and/or those living in low oxygen environments tend to have the functional properties of hemoglobin modulated by a high affinity for oxygen (Powers 1980;Wells 2009;Brunori 2014).…”

“…The oxygen transport in the blood may depend directly on (i) the number of circulating red blood cells and hemoglobin concentration and (ii) the functional properties of hemoglobin and its allosteric modulators (Nikinmaa & Soivio 2005;Brunori 2014). It has been reported that active swimming fish have more circulating red cell blood and high hemoglobin levels, while sluggish fish and/or those living in low oxygen environments tend to have the functional properties of hemoglobin modulated by a high affinity for oxygen (Powers 1980;Wells 2009;Brunori 2014). Considering all the arguments outlined above, there is support for the concept of symmorphosis, which is the capacity of structural elements to match but not exceed the functional requirements of an animal (Weibel 2000).…”

New Insights into Active Site Conformation Dynamics of E. coli PNP Revealed by Combined H/D Exchange Approach and Molecular Dynamics Simulations

“…to get insight into relations between protein dynamics and biological functions [4].The thoroughly studied example is hemoglobin allostery with positive cooperativity between subunits [5,6]. The versatile approaches used for these studies involve time-resolved protein crystallography based on recently introduced X-ray free electron laser method (XFEL) suitable to resolve dynamics, particularly related to proton transfer through H-bonds, at ultrafast time (femtosecond) scale [7].…”