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Interdomain linkers tailor the stability of immunoglobulin repeats in polyproteins

Abstract : Linkers in polyproteins are considered as mere spacers between two adjacent domains. However, a series of studies using single-molecule force spectroscopy have recently reported distinct thermodynamic stability of I27 in polyproteins with varying linkers and indicated the vital role of linkers in domain stability. A flexible glycine rich linker (-(GGG)n, n≥3) featured unfolding at lower forces than regularly used arg-ser (RS) based linker. Interdomain interactions among I27 domains in Gly-rich linkers were suggested to lead to reduced domain stability. However, the negative impact of inter domain interactions on domain stability is thermodynamically counter-intuitive and demanded thorough investigations. Here, using an array of ensemble equilibrium experiments and in-silico measurements with I27 singlet and doublets with two aforementioned linkers, we delineate that the inter-domain interactions in fact raise the stability of the polyprotein with RS linker. More surprisingly, a highly flexible Gly-rich linker has no interference on the stability of polyprotein. Overall, we conclude that flexible linkers are preferred in a polyprotein for maintaining domain's independence.
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Contributor : Juan Cortés Connect in order to contact the contributor
Submitted on : Sunday, March 7, 2021 - 9:41:57 AM
Last modification on : Friday, August 5, 2022 - 10:49:11 AM
Long-term archiving on: : Tuesday, June 8, 2021 - 6:03:19 PM


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Tanuja Joshi, Surbhi Garg, Alejandro Estaña, Juan Cortés, Pau Bernadó, et al.. Interdomain linkers tailor the stability of immunoglobulin repeats in polyproteins. Biochemical and Biophysical Research Communications, Elsevier, 2021, 550, pp.43-48. ⟨10.1016/j.bbrc.2021.02.114⟩. ⟨hal-03161535⟩



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