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Proc Natl Acad Sci U S A
2023 Oct 10;12041:e2301207120. doi: 10.1073/pnas.2301207120.
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Molecular determinants for cold adaptation in an Antarctic Na+/K+-ATPase.
Galarza-Muñoz G
,
Soto-Morales SI
,
Jiao S
,
Holmgren M
,
Rosenthal JJC
.
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Enzymes from ectotherms living in chronically cold environments have evolved structural innovations to overcome the effects of temperature on catalysis. Cold adaptation of soluble enzymes is driven by changes within their primary structure or the aqueous milieu. For membrane-embedded enzymes, like the Na+/K+-ATPase, the situation is different because changes to the lipid bilayer in which they operate may also be relevant. Although much attention has been focused on thermal adaptation within lipid bilayers, relatively little is known about the contribution of structural changes within membrane-bound enzymes themselves. The identification of specific mutations that confer temperature compensation is complicated by the presence of neutral mutations, which can be more numerous. In the present study, we identified specific amino acids in a Na+/K+-ATPase from an Antarctic octopus that underlie cold resistance. Our approach was to generate chimeras between an Antarctic clone and a temperate ortholog and then study their temperature sensitivities in Xenopus oocytes using an electrophysiological approach. We identified 12 positions in the Antarctic Na+/K+-ATPase that, when transferred to the temperate ortholog, were sufficient to confer cold tolerance. Furthermore, although all 12 Antarctic mutations were required for the full phenotype, a single leucine in the third transmembrane segment (M3) imparted most of it. Mutations that confer cold resistance are mostly in transmembrane segments, at positions that face the lipid bilayer. We propose that the interface between a transmembrane enzyme and the lipid bilayer is a critical determinant of temperature sensitivity and, accordingly, has been a prime evolutionary target for thermal adaptation.
2 U54 NS039405-06 HHS | NIH | Office of Extramural Research, National Institutes of Health (OER), NS064259 HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), 0344070 National Science Foundation (NSF), 2G12RR003051 HHS | NIH | National Center for Research Resources (NCRR), 8G12MD007600 HHS | NIH | National Institute on Minority Health and Health Disparities (NIMHD), Intramural support HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), U54 NS039405 NINDS NIH HHS , R01 NS064259 NINDS NIH HHS , G12 MD007600 NIMHD NIH HHS, G12 RR003051 NCRR NIH HHS
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