The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins

Alexei V. Korennykh; Joseph A. Piccirilli; Carl C. Correll

doi:10.1038/nsmb1082

The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins

Alexei V. Korennykh, Joseph A. Piccirilli, Carl C. Correll

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

α-sarcin ribotoxins comprise a unique family of ribonucleases that cripple the ribosome by catalyzing endoribonucleolytic cleavage of ribosomal RNA at a specific location in the sarcin/ricin loop (SRL). The SRL structure alone is cleaved site-specifically by the ribotoxin, but the ribosomal context enhances the reaction rate by several orders of magnitude. We show that, for the α-sarcin-like ribotoxin restrictocin, this catalytic advantage arises from favorable electrostatic interactions with the ribosome. Restrictocin binds at many sites on the ribosomal surface and under certain conditions cleaves the SRL with a second-order rate constant of 1.7 × 10¹⁰ M ^-1 s^-1, a value that matches the predicted frequency of random restrictocin-ribosome encounters. The results suggest a mechanism of target location whereby restrictocin encounters ribosomes randomly and diffuses within the ribosomal electrostatic field to the SRL. These studies show a role for electrostatics in protein-ribosome recognition.

Original language	English (US)
Pages (from-to)	436-443
Number of pages	8
Journal	Nature Structural and Molecular Biology
Volume	13
Issue number	5
DOIs	https://doi.org/10.1038/nsmb1082
State	Published - May 14 2006
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Structural Biology

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title = "The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins",

abstract = "α-sarcin ribotoxins comprise a unique family of ribonucleases that cripple the ribosome by catalyzing endoribonucleolytic cleavage of ribosomal RNA at a specific location in the sarcin/ricin loop (SRL). The SRL structure alone is cleaved site-specifically by the ribotoxin, but the ribosomal context enhances the reaction rate by several orders of magnitude. We show that, for the α-sarcin-like ribotoxin restrictocin, this catalytic advantage arises from favorable electrostatic interactions with the ribosome. Restrictocin binds at many sites on the ribosomal surface and under certain conditions cleaves the SRL with a second-order rate constant of 1.7 × 1010 M -1 s-1, a value that matches the predicted frequency of random restrictocin-ribosome encounters. The results suggest a mechanism of target location whereby restrictocin encounters ribosomes randomly and diffuses within the ribosomal electrostatic field to the SRL. These studies show a role for electrostatics in protein-ribosome recognition.",

author = "Korennykh, {Alexei V.} and Piccirilli, {Joseph A.} and Correll, {Carl C.}",

note = "Funding Information: We are grateful to Y.-L. Chan for valuable advice and discussion, J. Olvera for excellent technical assistance and M. Yousef for the help at the Biophysical Core Facility at the University of Chicago. We thank I.G. Wool, P.B. Moore and members of the Piccirilli laboratory for helpful comments on the manuscript. This work was supported by grants from the Burroughs Wellcome Fund to A.V.K., from the Howard Hughes Medical Institute to J.A.P. and from the US National Institutes of Health (GM59782) to C.C.C.",

year = "2006",

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AU - Korennykh, Alexei V.

AU - Piccirilli, Joseph A.

AU - Correll, Carl C.

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PY - 2006/5/14

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N2 - α-sarcin ribotoxins comprise a unique family of ribonucleases that cripple the ribosome by catalyzing endoribonucleolytic cleavage of ribosomal RNA at a specific location in the sarcin/ricin loop (SRL). The SRL structure alone is cleaved site-specifically by the ribotoxin, but the ribosomal context enhances the reaction rate by several orders of magnitude. We show that, for the α-sarcin-like ribotoxin restrictocin, this catalytic advantage arises from favorable electrostatic interactions with the ribosome. Restrictocin binds at many sites on the ribosomal surface and under certain conditions cleaves the SRL with a second-order rate constant of 1.7 × 1010 M -1 s-1, a value that matches the predicted frequency of random restrictocin-ribosome encounters. The results suggest a mechanism of target location whereby restrictocin encounters ribosomes randomly and diffuses within the ribosomal electrostatic field to the SRL. These studies show a role for electrostatics in protein-ribosome recognition.

AB - α-sarcin ribotoxins comprise a unique family of ribonucleases that cripple the ribosome by catalyzing endoribonucleolytic cleavage of ribosomal RNA at a specific location in the sarcin/ricin loop (SRL). The SRL structure alone is cleaved site-specifically by the ribotoxin, but the ribosomal context enhances the reaction rate by several orders of magnitude. We show that, for the α-sarcin-like ribotoxin restrictocin, this catalytic advantage arises from favorable electrostatic interactions with the ribosome. Restrictocin binds at many sites on the ribosomal surface and under certain conditions cleaves the SRL with a second-order rate constant of 1.7 × 1010 M -1 s-1, a value that matches the predicted frequency of random restrictocin-ribosome encounters. The results suggest a mechanism of target location whereby restrictocin encounters ribosomes randomly and diffuses within the ribosomal electrostatic field to the SRL. These studies show a role for electrostatics in protein-ribosome recognition.

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The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins

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