TY - JOUR
T1 - Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO2
AU - Fago, Angela
AU - Natarajan, Chandrasekhar
AU - Pettinati, Martín
AU - Hoffmann, Federico G.
AU - Wang, Tobias
AU - Weber, Roy E.
AU - Drusin, Salvador I.
AU - Issoglio, Federico
AU - Martí, Marcelo A.
AU - Estrin, Darío
AU - Storz, Jay F.
PY - 2020
Y1 - 2020
N2 - Hemoglobins (Hbs) of crocodilians are reportedly characterized by unique mechanisms of allosteric regulatory control, but there are conflicting reports regarding the importance of different effectors, such as chloride ions, organic phosphates, and CO2. Progress in understanding the unusual properties of crocodilian Hbs has also been hindered by a dearth of structural information. Here, we present the first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species. We examine mechanisms of allosteric regulation in the Hbs of 13 crocodilian species belonging to the families Crocodylidae and Alligatoridae. We also report new amino acid sequences for the α- and β-globins of these taxa, which, in combination with structural analyses, provide insights into molecular mechanisms of allosteric regulation. All crocodilian Hbs exhibited a remarkably strong sensitivity to CO2, which would permit effective O2 unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O2-affinities, there is considerable variation in sensitivity to Cl- ions and ATP, which appears to be at least partly attributable to variation in the extent of NH2-terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O2 affinity only in caimans. Modeling suggests that allosteric ATP binding has a somewhat different structural basis in crocodilian and mammalian Hbs.
AB - Hemoglobins (Hbs) of crocodilians are reportedly characterized by unique mechanisms of allosteric regulatory control, but there are conflicting reports regarding the importance of different effectors, such as chloride ions, organic phosphates, and CO2. Progress in understanding the unusual properties of crocodilian Hbs has also been hindered by a dearth of structural information. Here, we present the first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species. We examine mechanisms of allosteric regulation in the Hbs of 13 crocodilian species belonging to the families Crocodylidae and Alligatoridae. We also report new amino acid sequences for the α- and β-globins of these taxa, which, in combination with structural analyses, provide insights into molecular mechanisms of allosteric regulation. All crocodilian Hbs exhibited a remarkably strong sensitivity to CO2, which would permit effective O2 unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O2-affinities, there is considerable variation in sensitivity to Cl- ions and ATP, which appears to be at least partly attributable to variation in the extent of NH2-terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O2 affinity only in caimans. Modeling suggests that allosteric ATP binding has a somewhat different structural basis in crocodilian and mammalian Hbs.
KW - adaptation
KW - allostery
KW - blood
KW - oxygen transport
KW - reptile
UR - http://www.scopus.com/inward/record.url?scp=85081944394&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00342.2019
DO - 10.1152/ajpregu.00342.2019
M3 - Journal article
C2 - 32022587
AN - SCOPUS:85081944394
SN - 0363-6119
VL - 318
SP - R657-R667
JO - American journal of physiology. Regulatory, integrative and comparative physiology
JF - American journal of physiology. Regulatory, integrative and comparative physiology
IS - 3
ER -