An erythroid chaperone that facilitates folding of α-globin subunits for hemoglobin synthesis

Xiang Yu, Yi Kong, Louis C. Dore, Osheiza Abdulmalik, Anne M. Katein, Suiping Zhou, John K. Choi, David Gell, Joel P. Mackay, Andrew J. Gow, Mitchell J. Weiss

Результат исследований: Материалы для журналаСтатья

81 Цитирования (Scopus)

Аннотация

Erythrocyte precursors produce abundant α- and β-globin proteins, which assemble with each other to form hemoglobin A (HbA), the major blood oxygen carrier. αHb-stabilizing protein (AHSP) binds free α subunits reversibly to maintain their structure and limit their ability to generate reactive oxygen species. Accordingly, loss of AHSP aggravates the toxicity of excessive free α-globin caused by β-globin gene disruption in mice. Surprisingly, we found that AHSP also has important functions when free α-globin is limited. Thus, compound mutants lacking both Ahsp and 1 of 4 α-globin genes (genotype Ahsp-/-α-globin -/-α/αα) exhibited more severe anemia and Hb instability than mice with either mutation alone. In vitro, recombinant AHSP promoted folding of newly translated α-globin, enhanced its refolding after denaturation, and facilitated its incorporation into HbA. Moreover, in erythroid precursors, newly formed free α-globin was destabilized by loss of AHSP. Therefore, in addition to its previously defined role in detoxification of excess α-globin, AHSP also acts as a molecular chaperone to stabilize nascent α-globin for HbA assembly. Our findings illustrate what we believe to be a novel adaptive mechanism by which a specialized cell coordinates high-level production of a multisubunit protein and protects against various synthetic imbalances.

Язык оригиналаАнглийский
Страницы (с-по)1856-1865
Число страниц10
ЖурналJournal of Clinical Investigation
Том117
Номер выпуска7
DOI
СостояниеОпубликовано - 2 июл 2007
Опубликовано для внешнего пользованияДа

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Цитировать

Yu, X., Kong, Y., Dore, L. C., Abdulmalik, O., Katein, A. M., Zhou, S., Choi, J. K., Gell, D., Mackay, J. P., Gow, A. J., & Weiss, M. J. (2007). An erythroid chaperone that facilitates folding of α-globin subunits for hemoglobin synthesis. Journal of Clinical Investigation, 117(7), 1856-1865. https://doi.org/10.1172/JCI31664