4HRH

Crystal Structure of p11-Annexin A2(N-terminal) Fusion Protein in Complex with SMARCA3 Peptide

Summary for 4HRH

• Entry DOI: 10.2210/pdb4hrh/pdb
• Descriptor: Protein S100-A10, Annexin A2, Helicase-like transcription factor, SULFATE ION (3 entities in total)
• Functional Keywords: ef-hand, calcium-binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space, extracellular matrix, basement membrane : P07355; Cytoplasm : Q14527
• Total number of polymer chains: 4
• Total formula weight: 30687.07

Authors

Gao, P.,Patel, D.J. (deposition date: 2012-10-27, release date: 2013-03-06, Last modification date: 2023-09-20)

Primary citation

Oh, Y.S.,Gao, P.,Lee, K.W.,Ceglia, I.,Seo, J.S.,Zhang, X.,Ahn, J.H.,Chait, B.T.,Patel, D.J.,Kim, Y.,Greengard, P.
SMARCA3, a Chromatin-Remodeling Factor, Is Required for p11-Dependent Antidepressant Action.
Cell(Cambridge,Mass.), 152:831-843, 2013

PubMed Abstract: p11, through unknown mechanisms, is required for behavioral and cellular responses to selective serotonin reuptake inhibitors (SSRIs). We show that SMARCA3, a chromatin-remodeling factor, is a target for the p11/annexin A2 heterotetrameric complex. Determination of the crystal structure indicates that SMARCA3 peptide binds to a hydrophobic pocket in the heterotetramer. Formation of this complex increases the DNA-binding affinity of SMARCA3 and its localization to the nuclear matrix fraction. In the dentate gyrus, both p11 and SMARCA3 are highly enriched in hilar mossy cells and basket cells. The SSRI fluoxetine induces expression of p11 in both cell types and increases the amount of the ternary complex of p11/annexin A2/SMARCA3. SSRI-induced neurogenesis and behavioral responses are abolished by constitutive knockout of SMARCA3. Our studies indicate a central role for a chromatin-remodeling factor in the SSRI/p11 signaling pathway and suggest an approach to the development of improved antidepressant therapies. PAPERCLIP:

PubMed: 23415230
DOI: 10.1016/j.cell.2013.01.014

Experimental method

X-RAY DIFFRACTION (3.001 Å)