2P8V

Crystal structure of human Homer3 EVH1 domain

Summary for 2P8V

• Entry DOI: 10.2210/pdb2p8v/pdb
• Descriptor: Homer protein homolog 3, SULFATE ION (3 entities in total)
• Functional Keywords: homer3, evh1 domain, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9NSC5
• Total number of polymer chains: 1
• Total formula weight: 13270.87

Authors

Bouyain, S.,Tu, J.,Huang, G.N.,Worley, P.F.,Leahy, D. (deposition date: 2007-03-23, release date: 2007-11-20, Last modification date: 2023-08-30)

Primary citation

Huang, G.N.,Huso, D.L.,Bouyain, S.,Tu, J.,McCorkell, K.A.,May, M.J.,Zhu, Y.,Lutz, M.,Collins, S.,Dehoff, M.,Kang, S.,Whartenby, K.,Powell, J.,Leahy, D.,Worley, P.F.
NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins.
Science, 319:476-481, 2008

PubMed Abstract: 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.

PubMed: 18218901
DOI: 10.1126/science.1151227

Experimental method

X-RAY DIFFRACTION (1.85 Å)