High-pressure SAXS, deep life, and extreme biophysics

Gillilan, Richard E.

doi:10.1016/bs.mie.2022.08.025

Cited by 2 publications

(2 citation statements)

References 78 publications

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“…The HP-SAXS data were collected at the sector 7A1 station (HP-Bio) of the Cornell High Energy Synchrotron Source (CHESS) (52)(53)(54). Pressure was maintained by a Barocycler HUB440 high-pressure pump (Pressure BioSciences).…”

Section: High-pressure Saxsmentioning

confidence: 99%

Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions

Levengood,

Potoyan,

Penumutchu

et al. 2024

Sci. Adv.

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The functional properties of RNA binding proteins (RBPs) require allosteric regulation through interdomain communication. Despite the importance of allostery to biological regulation, only a few studies have been conducted to describe the biophysical nature by which interdomain communication manifests in RBPs. Here, we show for hnRNP A1 that interdomain communication is vital for the unique stability of its amino-terminal domain, which consists of two RNA recognition motifs (RRMs). These RRMs exhibit drastically different stability under pressure. RRM2 unfolds as an individual domain but remains stable when appended to RRM1. Variants that disrupt interdomain communication between the tandem RRMs show a significant decrease in stability. Carrying these mutations over to the full-length protein for in vivo experiments revealed that the mutations affected the ability of the disordered carboxyl-terminal domain to engage in protein-protein interactions and influenced the protein’s RNA binding capacity. Collectively, this work reveals that thermodynamic coupling between the tandem RRMs of hnRNP A1 accounts for its allosteric regulatory functions.

show abstract

Section: High-pressure Saxsmentioning

confidence: 99%

Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions

Levengood,

Potoyan,

Penumutchu

et al. 2024

Sci. Adv.

View full text Add to dashboard Cite

show abstract

“…The HP-SAXS data were collected at the Sector 7A1 station (HP-Bio) of the Cornell High Energy Synchrotron Source (CHESS) [49][50][51]. Pressure was maintained by a Barocycler HUB440 high-pressure pump (Pressure BioSciences).…”

Section: High-pressure Saxsmentioning

confidence: 99%

Thermodynamic Coupling of the tandem RRM domains of hnRNP A1 underlie its Pleiotropic RNA Binding Functions

Levengood,

Potoyan,

Penumutchu

et al. 2023

Preprint

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The functional properties of RNA-binding proteins (RBPs) require allosteric regulation through inter-domain communication. Despite the foundational importance of allostery to biological regulation, almost no studies have been conducted to describe the biophysical nature by which inter-domain communication manifests in RBPs. Here, we show through high-pressure studies with hnRNP A1 that inter-domain communication is vital for the unique stability of its N-terminal domain containing a tandem of RNA Recognition Motifs (RRMs). Despite high sequence similarity and nearly identical tertiary structures, the two RRMs exhibit drastically different stability under pressure. RRM2 unfolds completely under high-pressure as an individual domain, but when appended to RRM1, it remains stable. Variants in which inter-domain communication is disrupted between the tandem RRMs show a large decrease in stability under pressure. Carrying these mutations over to the full-length protein for in vivo experiments revealed that the mutations affected the ability of the disordered C-terminus to engage in protein-protein interactions and more importantly, they also influenced the RNA binding capacity. Collectively, this work reveals that thermodynamic coupling between the tandem RRMs of hnRNP A1 accounts for its allosteric regulatory functions.

show abstract

High-pressure SAXS, deep life, and extreme biophysics

Cited by 2 publications

References 78 publications

Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions

Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions

Thermodynamic Coupling of the tandem RRM domains of hnRNP A1 underlie its Pleiotropic RNA Binding Functions

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