2p8v

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2p8v, resolution 1.850Å

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Crystal structure of human Homer3 EVH1 domain

Overview

T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate, in activating T cells, although understanding of how these pathways are, themselves regulated is incomplete. We found that Homer2 and Homer3, members of the Homer family of cytoplasmic scaffolding proteins, are, negative regulators of T cell activation. This is achieved through binding, of nuclear factor of activated T cells (NFAT) and by competing with, calcineurin. Homer-NFAT binding was also antagonized by active, serine-threonine kinase AKT, thereby enhancing TCR signaling via, calcineurin-dependent dephosphorylation of NFAT. This corresponded with, changes in cytokine expression and an increase in effector-memory T cell, populations in Homer-deficient mice, which also developed autoimmune-like, pathology. These results demonstrate a further means by which, costimulatory signals are regulated to control self-reactivity.

About this Structure

2P8V is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins., Huang GN, Huso DL, Bouyain S, Tu J, McCorkell KA, May MJ, Zhu Y, Lutz M, Collins S, Dehoff M, Kang S, Whartenby K, Powell J, Leahy D, Worley PF, Science. 2008 Jan 25;319(5862):476-81. PMID:18218901

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