UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Mechanism of β-actin mRNA Recognition by ZBP1

Nicastro, G; Candel, AM; Uhl, M; Oregioni, A; Hollingworth, D; Backofen, R; Martin, SR; (2017) Mechanism of β-actin mRNA Recognition by ZBP1. Cell Reports , 18 (5) pp. 1187-1199. 10.1016/j.celrep.2016.12.091. Green open access

[thumbnail of Ramos_1-s2.0-S2211124717300013-main.pdf]
Preview
Text
Ramos_1-s2.0-S2211124717300013-main.pdf - Published Version

Download (3MB) | Preview

Abstract

Zipcode binding protein 1 (ZBP1) is an oncofetal RNA-binding protein that mediates the transport and local translation of β-actin mRNA by the KH3-KH4 di-domain, which is essential for neuronal development. The high-resolution structures of KH3-KH4 with their respective target sequences show that KH4 recognizes a non-canonical GGA sequence via an enlarged and dynamic hydrophobic groove, whereas KH3 binding to a core CA sequence occurs with low specificity. A data-informed kinetic simulation of the two-step binding reaction reveals that the overall reaction is driven by the second binding event and that the moderate affinities of the individual interactions favor RNA looping. Furthermore, the concentration of ZBP1, but not of the target RNA, modulates the interaction, which explains the functional significance of enhanced ZBP1 expression during embryonic development.

Type: Article
Title: Mechanism of β-actin mRNA Recognition by ZBP1
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.12.091
Publisher version: http://doi.org/10.1016/j.celrep.2016.12.091
Language: English
Additional information: © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Protein-RNA interactions; NMR; binding mechanism; neuronal mRNA granules; neuronal development; mRNA local translation; ZBP1; IMP1
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1539843
Downloads since deposit
102Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item