期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 99, 期 13, 页码 8479-8483出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.122055299
关键词
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资金
- NHLBI NIH HHS [R01 HL58038] Funding Source: Medline
We show that in solutions of human hemoglobin (Hb)-oxy- and deoxy-Hb A or S-of near-physiological pH, ionic strength, and Hb concentration, liquid-liquid phase separation occurs reversibly and reproducibly at temperatures between 35 and 40degreesC. In solutions of deoxy-HbS, we demonstrate that the dense liquid droplets facilitate the nucleation of HbS polymers, whose formation is the primary pathogenic event for sickle cell anemia. In view of recent results that shifts of the liquid-liquid separation phase boundary can be achieved by nontoxic additives at molar concentrations up to 30 times lower than the protein concentrations, these findings open new avenues for the inhibition of the HbS polymerization.
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