Structure of human Sp140 PHD finger: An atypical fold interacting with Pin1

Chiara Zucchelli, Simone Tamburri, Giacomo Quilici, Eleonora Palagano, Andrea Berardi, Mario Saare, Pärt Peterson, Angela Bachi, Giovanna Musco

Research output: Contribution to journalArticle

Abstract

Sp140 is a nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. The presence of several chromatin related modules such as plant homeodomain (PHD), bromodomain and SAND domain suggests a role in chromatin-mediated regulation of gene expression; however, its real function is still elusive. Herein we present the solution structure of Sp140-PHD finger and investigate its role as epigenetic reader in vitro. Sp140-PHD presents an atypical PHD finger fold which does not bind to histone H3 tails but is recognized by peptidylprolyl isomerase Pin1. Pin1 specifically binds to a phosphopeptide corresponding to the L3 loop of Sp140-PHD and catalyzes cis-trans isomerization of a pThr-Pro bond. Moreover co-immunoprecipitation experiments demonstrate FLAG-Sp140 interaction with endogenous Pin1 in vivo. Overall these data include Sp140 in the list of the increasing number of Pin1 binders and expand the regulatory potential of PHD fingers as versatile structural platforms for diversified interactions.

Original languageEnglish
Pages (from-to)216-231
Number of pages16
JournalFEBS Journal
Volume281
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • histones
  • nmr
  • phd finger
  • pin1
  • sp140

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Zucchelli, C., Tamburri, S., Quilici, G., Palagano, E., Berardi, A., Saare, M., Peterson, P., Bachi, A., & Musco, G. (2014). Structure of human Sp140 PHD finger: An atypical fold interacting with Pin1. FEBS Journal, 281(1), 216-231. https://doi.org/10.1111/febs.12588