Cotranslational folding cooperativity of contiguous domains of α-spectrin

Proceedings of the National Academy of Sciences of the United States of America
Grant KempGunnar von Heijne

Abstract

Proteins synthesized in the cell can begin to fold during translation before the entire polypeptide has been produced, which may be particularly relevant to the folding of multidomain proteins. Here, we study the cotranslational folding of adjacent domains from the cytoskeletal protein α-spectrin using force profile analysis (FPA). Specifically, we investigate how the cotranslational folding behavior of the R15 and R16 domains are affected by their neighboring R14 and R16, and R15 and R17 domains, respectively. Our results show that the domains impact each other's folding in distinct ways that may be important for the efficient assembly of α-spectrin, and may reduce its dependence on chaperones. Furthermore, we directly relate the experimentally observed yield of full-length protein in the FPA assay to the force exerted by the folding protein in piconewtons. By combining pulse-chase experiments to measure the rate at which the arrested protein is converted into full-length protein with a Bell model of force-induced rupture, we estimate that the R16 domain exerts a maximal force on the nascent chain of ∼15 pN during cotranslational folding.

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Citations

Feb 6, 2021·Biological Chemistry·Frederik BarbarinoMiriam M Cortese-Krott
Apr 24, 2021·Frontiers in Genetics·Ruifang LiYongxia Cheng
May 7, 2021·Communications Biology·Florian WruckAlexandros Katranidis
May 15, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kevin MaciubaChristian M Kaiser
May 15, 2021·Journal of Molecular Biology·Hena SandhuGunnar von Heijne
Jun 12, 2021·Frontiers in Molecular Biosciences·Jiří KoubekGünter Kramer
Nov 24, 2021·Biophysical Journal·John M McBride, Tsvi Tlusty
Jan 8, 2022·The EMBO Journal·Xabier AgirrezabalaMarina V Rodnina

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