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Title: Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [2];  [1];  [1]; ORCiD logo [1];  [3]
  1. Univ. of Nebraska, Lincoln, NE (United States)
  2. Japan Synchrotron Radiation Research Inst., Sayo (Japan)
  3. Russian Academy of Medical Sciences (Russian Federation)
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Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant. Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules. The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Inst. of Health/National Heart, Lung, and Blood Inst.
OSTI ID:
1349928
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 3 Vol. 12; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (1)

Acclimatization of low altitude-bred deer mice ( Peromyscus maniculatus ) to high altitude journal November 2018

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59 BASIC BIOLOGICAL SCIENCES
hemoglobin
crystal structure
crystals
deer
heme
oxygen
diffraction
data processing