4hre

Crystal Structure of p11/Annexin A2 Heterotetramer in Complex with SMARCA3 PeptideCrystal Structure of p11/Annexin A2 Heterotetramer in Complex with SMARCA3 Peptide

Structural highlights

4hre is a 12 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Anxa2, Anx2, Cal1h (LK3 transgenic mice), S100A10, ANX2LG, CAL1L, CLP11 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ANXA2_MOUSE] Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. [HLTF_HUMAN] Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [S10AA_HUMAN] Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.

Publication Abstract from PubMed

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:

SMARCA3, a Chromatin-Remodeling Factor, Is Required for p11-Dependent Antidepressant Action.,Oh YS, Gao P, Lee KW, Ceglia I, Seo JS, Zhang X, Ahn JH, Chait BT, Patel DJ, Kim Y, Greengard P Cell. 2013 Feb 14;152(4):831-43. doi: 10.1016/j.cell.2013.01.014. PMID:23415230^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ding H, Benotmane AM, Suske G, Collen D, Belayew A. Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene. J Biol Chem. 1999 Jul 9;274(28):19573-80. PMID:10391891
↑ Unk I, Hajdu I, Fatyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L. Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3768-73. doi:, 10.1073/pnas.0800563105. Epub 2008 Mar 3. PMID:18316726 doi:http://dx.doi.org/10.1073/pnas.0800563105
↑ Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105
↑ Sheridan PL, Schorpp M, Voz ML, Jones KA. Cloning of an SNF2/SWI2-related protein that binds specifically to the SPH motifs of the SV40 enhancer and to the HIV-1 promoter. J Biol Chem. 1995 Mar 3;270(9):4575-87. PMID:7876228
↑ Ding H, Descheemaeker K, Marynen P, Nelles L, Carvalho T, Carmo-Fonseca M, Collen D, Belayew A. Characterization of a helicase-like transcription factor involved in the expression of the human plasminogen activator inhibitor-1 gene. DNA Cell Biol. 1996 Jun;15(6):429-42. PMID:8672239
↑ Gong X, Kaushal S, Ceccarelli E, Bogdanova N, Neville C, Nguyen T, Clark H, Khatib ZA, Valentine M, Look AT, Rosenthal N. Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Dev Biol. 1997 Mar 15;183(2):166-82. PMID:9126292 doi:http://dx.doi.org/10.1006/dbio.1996.8486
↑ Oh YS, Gao P, Lee KW, Ceglia I, Seo JS, Zhang X, Ahn JH, Chait BT, Patel DJ, Kim Y, Greengard P. SMARCA3, a Chromatin-Remodeling Factor, Is Required for p11-Dependent Antidepressant Action. Cell. 2013 Feb 14;152(4):831-43. doi: 10.1016/j.cell.2013.01.014. PMID:23415230 doi:http://dx.doi.org/10.1016/j.cell.2013.01.014

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OCA

[1] Ding H, Benotmane AM, Suske G, Collen D, Belayew A. Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene. J Biol Chem. 1999 Jul 9;274(28):19573-80. PMID:10391891

[2] Unk I, Hajdu I, Fatyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L. Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3768-73. doi:, 10.1073/pnas.0800563105. Epub 2008 Mar 3. PMID:18316726 doi:http://dx.doi.org/10.1073/pnas.0800563105

[3] Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105

[4] Sheridan PL, Schorpp M, Voz ML, Jones KA. Cloning of an SNF2/SWI2-related protein that binds specifically to the SPH motifs of the SV40 enhancer and to the HIV-1 promoter. J Biol Chem. 1995 Mar 3;270(9):4575-87. PMID:7876228

[5] Ding H, Descheemaeker K, Marynen P, Nelles L, Carvalho T, Carmo-Fonseca M, Collen D, Belayew A. Characterization of a helicase-like transcription factor involved in the expression of the human plasminogen activator inhibitor-1 gene. DNA Cell Biol. 1996 Jun;15(6):429-42. PMID:8672239

[6] Gong X, Kaushal S, Ceccarelli E, Bogdanova N, Neville C, Nguyen T, Clark H, Khatib ZA, Valentine M, Look AT, Rosenthal N. Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Dev Biol. 1997 Mar 15;183(2):166-82. PMID:9126292 doi:http://dx.doi.org/10.1006/dbio.1996.8486

[7] Oh YS, Gao P, Lee KW, Ceglia I, Seo JS, Zhang X, Ahn JH, Chait BT, Patel DJ, Kim Y, Greengard P. SMARCA3, a Chromatin-Remodeling Factor, Is Required for p11-Dependent Antidepressant Action. Cell. 2013 Feb 14;152(4):831-43. doi: 10.1016/j.cell.2013.01.014. PMID:23415230 doi:http://dx.doi.org/10.1016/j.cell.2013.01.014

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