Interdomain linkers tailor the stability of immunoglobulin repeats in polyproteins - Archive ouverte HAL Access content directly
Journal Articles Biochemical and Biophysical Research Communications Year : 2021

Interdomain linkers tailor the stability of immunoglobulin repeats in polyproteins

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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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Dates and versions

hal-03161535 , version 1 (07-03-2021)

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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, 2021, 550, pp.43-48. ⟨10.1016/j.bbrc.2021.02.114⟩. ⟨hal-03161535⟩
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