5SVE

Structure of Calcineurin in complex with NFATc1 LxVP peptide

Summary for 5SVE

• Entry DOI: 10.2210/pdb5sve/pdb
• Descriptor: Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, Calcineurin subunit B type 1, NFATc1 LxVP peptide, ... (7 entities in total)
• Functional Keywords: hydrolase, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 64451.75

Authors

Sheftic, S.R.,Page, R.,Peti, W. (deposition date: 2016-08-05, release date: 2017-01-11, Last modification date: 2023-10-04)

Primary citation

Sheftic, S.R.,Page, R.,Peti, W.
Investigating the human Calcineurin Interaction Network using the pi LxVP SLiM.
Sci Rep, 6:38920-38920, 2016

PubMed Abstract: Ser/thr phosphorylation is the primary reversible covalent modification of proteins in eukaryotes. As a consequence, it is the reciprocal actions of kinases and phosphatases that act as key molecular switches to fine tune cellular events. It has been well documented that ~400 human ser/thr kinases engage substrates via consensus phosphosite sequences. Strikingly, we know comparatively little about the mechanism by which ~40 human protein ser/thr phosphatases (PSPs) dephosphorylate ~15000 different substrates with high specificity. The identification of substrates of the essential PSP calcineurin (CN) has been exceptionally challenging and only a small fraction has been biochemically confirmed. It is now emerging that CN binds regulators and substrates via two short linear motifs (SLiMs), the well-studied PxIxIT SLiM and the LxVP SLiM, which remains controversial at the molecular level. Here we describe the crystal structure of CN in complex with its substrate NFATc1 and show that the LxVP SLiM is correctly defined as πɸLxVP. Bioinformatics studies using the πɸLxVP SLiM resulted in the identification of 567 potential CN substrates; a small subset was experimentally confirmed. This combined structural-bioinformatics approach provides a powerful method for dissecting the CN interaction network and for elucidating the role of CN in human health and disease.

PubMed: 27974827
DOI: 10.1038/srep38920

Experimental method

X-RAY DIFFRACTION (2.596 Å)