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Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex

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Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex. / Cardote, Teresa A F; Gadd, Morgan S; Ciulli, Alessio.

In: Structure, Vol. 25, No. 6, 06.06.2017, p. 901-911.e3.

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Cardote, Teresa A F ; Gadd, Morgan S ; Ciulli, Alessio. / Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex. In: Structure. 2017 ; Vol. 25, No. 6. pp. 901-911.e3.

Bibtex

@article{f7a3938d52004ae1b9fe27606d5a5736,
title = "Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex",
abstract = "Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting.",
keywords = "cullin-RING E3 ubiquitin ligases, protein-protein interactions, VHL, Cullin-2, RING domain proteins",
author = "Cardote, {Teresa A F} and Gadd, {Morgan S} and Alessio Ciulli",
note = "Copyright {\textcopyright} 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.",
year = "2017",
month = jun
day = "6",
doi = "10.1016/j.str.2017.04.009",
language = "English",
volume = "25",
pages = "901--911.e3",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex

AU - Cardote, Teresa A F

AU - Gadd, Morgan S

AU - Ciulli, Alessio

N1 - Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

PY - 2017/6/6

Y1 - 2017/6/6

N2 - Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting.

AB - Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting.

KW - cullin-RING E3 ubiquitin ligases

KW - protein-protein interactions

KW - VHL

KW - Cullin-2

KW - RING domain proteins

U2 - 10.1016/j.str.2017.04.009

DO - 10.1016/j.str.2017.04.009

M3 - Journal article

C2 - 28591624

VL - 25

SP - 901-911.e3

JO - Structure

JF - Structure

SN - 0969-2126

IS - 6

ER -