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Title: Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO 2
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 CO 2 . 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 CO 2 , which would permit effective O 2 unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O 2 -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 NH 2 -terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O 2 affinity only in caimans. Modeling suggests that allosteric ATP binding has a somewhat different structural basis in crocodilian and mammalian Hbs.  more » « less
Award ID(s):
1736249
NSF-PAR ID:
10179140
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Volume:
318
Issue:
3
ISSN:
0363-6119
Page Range / eLocation ID:
R657 to R667
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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