The p97-FAF1 protein complex reveals a common mode of p97 adaptor binding

 

Caroline A. Ewens, Silvia Panico, Patrik Kloppsteck, Ciaran McKeown, Ima-Obong Ebong, Carol Robinson, Xiaodong Zhang and Paul S. Freemont

The Journal of Biological Chemistry
2014 vol: 289 pp: 12077-12084 doi: 10.1074/jbc.M114.559591

Abstract

p97, also known as valosin-containing protein, is a versatile participant in the ubiquitin-proteasome system. p97 interacts with a large network of adaptor proteins to process ubiquitylated substrates in different cellular pathways, including endoplasmic reticulum-associated degradation and transcription factor activation. p97 and its adaptor Fas-associated factor-1 (FAF1) both have roles in the ubiquitin-proteasome system during NF-κB activation, although the mechanisms are unknown. FAF1 itself also has emerging roles in other cell-cycle pathways and displays altered expression levels in various cancer cell lines. We have performed a detailed study the p97-FAF1 interaction. We show that FAF1 binds p97 stably and in a stoichiometry of 3 to 6. Cryo-EM analysis of p97-FAF1 yielded a 17 Å reconstruction of the complex with FAF1 above the p97 ring. Characteristics of p97-FAF1 uncovered in this study reveal common features in the interactions of p97, providing mechanistic insight into how p97 mediates diverse functionalities.

View Publication

Topics: ATPases, Electron Microscopy (EM), Fas, Isothermal Titration Calorimetry, Protein Cross-linking, FAF1, p97, Proteins, Publications

Previous Article
Tunable stringency aptamer selection and gold nanoparticle assay for detection of cortisol
Tunable stringency aptamer selection and gold nanoparticle assay for detection of cortisol

Next Article
Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs
Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs