Structure of human S p140 PHD finger: an atypical fold interacting with P in1
Chiara Zucchellia b, Simone Tamburria b c d e f, Giacomo Quilicia b, Eleonora Palaganoc e, Andrea Berardia b, Mario Saareg h, Pärt Petersong h, Angela Bachic e, Giovanna Muscoa b✉
- aDulbecco Telethon Institute c/o Biomolecular NMR Laboratory S. Raffaele Scientific Institute Milano Italy
- bDulbecco Telethon Institute, c/o Biomolecular NMR Laboratory, S. Raffaele Scientific Institute, Milano, Italy
- cIFOM‐Firc Institute of Molecular Oncology Milano Italy
- dSan Raffaele Vita‐Salute University Milano Italy
- eIFOM-Firc Institute of Molecular Oncology, Milano, Italy
- fSan Raffaele Vita-Salute University, Milano, Italy
- gDepartment of Molecular Pathology Institute of Biomedicine and Translational Medicine University of Tartu Estonia
- hDepartment of Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia
- ✉Corresponding author
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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.
TL;DRThe solution structure of Sp140‐PHD finger is presented and its role as epigenetic reader in vitro is investigated and its inclusion in the list of the increasing number of Pin1 binders is expanded to expand the regulatory potential of PHD fingers as versatile structural platforms for diversified interactions. (Semantic Scholar)