Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO2

Angela Fago; Chandrasekhar Natarajan; Martín Pettinati; Federico G. Hoffmann; Tobias Wang; Roy E. Weber; Salvador I. Drusin; Federico Issoglio; Marcelo A. Martí; Darío Estrin; Jay F. Storz

doi:10.1152/ajpregu.00342.2019

Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO₂

Angela Fago, Chandrasekhar Natarajan, Martín Pettinati, Federico G. Hoffmann, Tobias Wang, Roy E. Weber, Salvador I. Drusin, Federico Issoglio, Marcelo A. Martí, Darío Estrin, Jay F. Storz

Institut for Biologi - Zoofysiologi

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

10 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	American journal of physiology. Regulatory, integrative and comparative physiology
Vol/bind	318
Nummer	3
Sider (fra-til)	R657-R667
Antal sider	11
ISSN	0363-6119
DOI	https://doi.org/10.1152/ajpregu.00342.2019
Status	Udgivet - 2020

Adgang til dokumentet

10.1152/ajpregu.00342.2019

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099459/

Andre filer og links

http://www.scopus.com/inward/record.url?scp=85081944394&partnerID=8YFLogxK

Citationsformater

Fago, A., Natarajan, C., Pettinati, M., Hoffmann, F. G., Wang, T., Weber, R. E., Drusin, S. I., Issoglio, F., Martí, M. A., Estrin, D., & Storz, J. F. (2020). Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO₂. American journal of physiology. Regulatory, integrative and comparative physiology, 318(3), R657-R667. https://doi.org/10.1152/ajpregu.00342.2019

@article{6217576ffe2744c1be6a5741493208cb,

title = "Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO2",

abstract = "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.",

keywords = "adaptation, allostery, blood, oxygen transport, reptile",

author = "Angela Fago and Chandrasekhar Natarajan and Mart{\'i}n Pettinati and Hoffmann, {Federico G.} and Tobias Wang and Weber, {Roy E.} and Drusin, {Salvador I.} and Federico Issoglio and Mart{\'i}, {Marcelo A.} and Dar{\'i}o Estrin and Storz, {Jay F.}",

year = "2020",

doi = "10.1152/ajpregu.00342.2019",

language = "English",

volume = "318",

pages = "R657--R667",

journal = "American journal of physiology. Regulatory, integrative and comparative physiology",

issn = "0363-6119",

publisher = "American Physiological Society",

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Fago, A, Natarajan, C, Pettinati, M, Hoffmann, FG, Wang, T , Weber, RE, Drusin, SI, Issoglio, F, Martí, MA, Estrin, D & Storz, JF 2020, 'Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO₂', American journal of physiology. Regulatory, integrative and comparative physiology, bind 318, nr. 3, s. R657-R667. https://doi.org/10.1152/ajpregu.00342.2019

Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP, and CO₂. / Fago, Angela; Natarajan, Chandrasekhar; Pettinati, Martín et al.
I: American journal of physiology. Regulatory, integrative and comparative physiology, Bind 318, Nr. 3, 2020, s. R657-R667.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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