Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1)

Alice Ballone; Federica Centorrino; Madita Wolter; Christian Ottmann

doi:10.1016/j.jsb.2018.01.011

Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1)

Alice Ballone, Federica Centorrino, Madita Wolter, Christian Ottmann

Chemical Biology

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

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Abstract

The deviant Ras activation machinery is found in approximately 30% of all human cancers. SOS1 is an important protagonist of this pathway that plays a key-role in aberrant cell proliferation and differentiation. Interaction of SOS1 with 14-3-3 proteins modulates SOS1 activity in Ras-MAPK signaling. In the present study, we analyze the 14-3-3/SOS1 protein-protein interaction (PPI) by different biochemical assays and report the high resolution crystal structure of a 13-mer motif of SOS1 bound to 14-3-3ζ. These structural and functional insights are important for the evaluation of this PPI interface for small-molecule stabilization as a new starting point for modulating the Ras-Raf-MAPK pathway.

Original language	English
Pages (from-to)	210-215
Number of pages	6
Journal	Journal of Structural Biology
Volume	202
Issue number	3
DOIs	https://doi.org/10.1016/j.jsb.2018.01.011
Publication status	Published - 1 Jun 2018

Keywords

Differential scanning fluorimetry
Fluorescence polarization
Isothermal titration calorimetry
Son of sevenless homolog 1
X-ray crystallography
Phosphorylation
Multiprotein Complexes/chemistry
Humans
SOS1 Protein/chemistry
Protein Binding
14-3-3 Proteins/chemistry
Cell Proliferation/genetics
Mutation
Protein Interaction Maps/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1)",

abstract = "The deviant Ras activation machinery is found in approximately 30% of all human cancers. SOS1 is an important protagonist of this pathway that plays a key-role in aberrant cell proliferation and differentiation. Interaction of SOS1 with 14-3-3 proteins modulates SOS1 activity in Ras-MAPK signaling. In the present study, we analyze the 14-3-3/SOS1 protein-protein interaction (PPI) by different biochemical assays and report the high resolution crystal structure of a 13-mer motif of SOS1 bound to 14-3-3ζ. These structural and functional insights are important for the evaluation of this PPI interface for small-molecule stabilization as a new starting point for modulating the Ras-Raf-MAPK pathway.",

keywords = "Differential scanning fluorimetry, Fluorescence polarization, Isothermal titration calorimetry, Son of sevenless homolog 1, X-ray crystallography, Phosphorylation, Multiprotein Complexes/chemistry, Humans, SOS1 Protein/chemistry, Protein Binding, 14-3-3 Proteins/chemistry, Cell Proliferation/genetics, Mutation, Protein Interaction Maps/genetics",

author = "Alice Ballone and Federica Centorrino and Madita Wolter and Christian Ottmann",

year = "2018",

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doi = "10.1016/j.jsb.2018.01.011",

language = "English",

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T1 - Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1)

AU - Ballone, Alice

AU - Centorrino, Federica

AU - Wolter, Madita

AU - Ottmann, Christian

PY - 2018/6/1

Y1 - 2018/6/1

N2 - The deviant Ras activation machinery is found in approximately 30% of all human cancers. SOS1 is an important protagonist of this pathway that plays a key-role in aberrant cell proliferation and differentiation. Interaction of SOS1 with 14-3-3 proteins modulates SOS1 activity in Ras-MAPK signaling. In the present study, we analyze the 14-3-3/SOS1 protein-protein interaction (PPI) by different biochemical assays and report the high resolution crystal structure of a 13-mer motif of SOS1 bound to 14-3-3ζ. These structural and functional insights are important for the evaluation of this PPI interface for small-molecule stabilization as a new starting point for modulating the Ras-Raf-MAPK pathway.

AB - The deviant Ras activation machinery is found in approximately 30% of all human cancers. SOS1 is an important protagonist of this pathway that plays a key-role in aberrant cell proliferation and differentiation. Interaction of SOS1 with 14-3-3 proteins modulates SOS1 activity in Ras-MAPK signaling. In the present study, we analyze the 14-3-3/SOS1 protein-protein interaction (PPI) by different biochemical assays and report the high resolution crystal structure of a 13-mer motif of SOS1 bound to 14-3-3ζ. These structural and functional insights are important for the evaluation of this PPI interface for small-molecule stabilization as a new starting point for modulating the Ras-Raf-MAPK pathway.

KW - Differential scanning fluorimetry

KW - Fluorescence polarization

KW - Isothermal titration calorimetry

KW - Son of sevenless homolog 1

KW - X-ray crystallography

KW - Phosphorylation

KW - Multiprotein Complexes/chemistry

KW - Humans

KW - SOS1 Protein/chemistry

KW - Protein Binding

KW - 14-3-3 Proteins/chemistry

KW - Cell Proliferation/genetics

KW - Mutation

KW - Protein Interaction Maps/genetics

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U2 - 10.1016/j.jsb.2018.01.011

DO - 10.1016/j.jsb.2018.01.011

M3 - Article

C2 - 29408703

AN - SCOPUS:85044622861

VL - 202

SP - 210

EP - 215

JO - Journal of Structural Biology

JF - Journal of Structural Biology

SN - 1047-8477

IS - 3

ER -

Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1)

Abstract

Keywords

UN SDGs

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