3unh

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Mouse 20S immunoproteasomeMouse 20S immunoproteasome

Structural highlights

3unh is a 28 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Activity:Proteasome endopeptidase complex, with EC number 3.4.25.1
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT
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Function

[PSA3_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSB8_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. May be involved in the inflammatory response pathway. Required for adipocyte differentiation.[1] [2] [3] [PSA7_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions (By similarity). The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions (By similarity). Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response (By similarity). [PSA6_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSB3_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSA4_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSB1_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSB9_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Contributes to NFKBIA degradation and subsequently NFKB1 generation.[4] [5] [PSB10_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Plays a role in determining the T-cell repertoire for an antiviral T-cell response.[6] [PSA2_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. [PSA5_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. [PSB2_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit has a chymotrypsin-like activity. [PSB4_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Mediates the lipopolysaccharide-induced signal macrophage proteasome. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity).[7] [PSA1_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Mediates the lipopolysaccharide-induced signal macrophage proteasome. Might be involved in the anti-inflammatory response of macrophages during the interaction with C.albicans heat-inactivated cells.[8] [9]

Publication Abstract from PubMed

Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 A resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit beta5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of beta5c/X but not beta5i, thereby explaining the selectivity of PR-957 for beta5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders.

Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity.,Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M Cell. 2012 Feb 17;148(4):727-38. PMID:22341445[10]

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

See Also

References

  1. ↑ Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K. A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J Clin Invest. 2011 Oct;121(10):4150-60. doi: 10.1172/JCI58414. Epub 2011 Sep 1. PMID:21881205 doi:http://dx.doi.org/10.1172/JCI58414
  2. ↑ Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell. 2012 Feb 17;148(4):727-38. PMID:22341445 doi:10.1016/j.cell.2011.12.030
  3. ↑ Fehling HJ, Swat W, Laplace C, Kuhn R, Rajewsky K, Muller U, von Boehmer H. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science. 1994 Aug 26;265(5176):1234-7. PMID:8066463
  4. ↑ Wang HX, Wang HM, Lin HY, Yang Q, Zhang H, Tsang BK, Zhu C. Proteasome subunit LMP2 is required for matrix metalloproteinase-2 and -9 expression and activities in human invasive extravillous trophoblast cell line. J Cell Physiol. 2006 Mar;206(3):616-23. PMID:16222703 doi:http://dx.doi.org/10.1002/jcp.20508
  5. ↑ Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell. 2012 Feb 17;148(4):727-38. PMID:22341445 doi:10.1016/j.cell.2011.12.030
  6. ↑ Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell. 2012 Feb 17;148(4):727-38. PMID:22341445 doi:10.1016/j.cell.2011.12.030
  7. ↑ Qureshi N, Perera PY, Shen J, Zhang G, Lenschat A, Splitter G, Morrison DC, Vogel SN. The proteasome as a lipopolysaccharide-binding protein in macrophages: differential effects of proteasome inhibition on lipopolysaccharide-induced signaling events. J Immunol. 2003 Aug 1;171(3):1515-25. PMID:12874245
  8. ↑ Qureshi N, Perera PY, Shen J, Zhang G, Lenschat A, Splitter G, Morrison DC, Vogel SN. The proteasome as a lipopolysaccharide-binding protein in macrophages: differential effects of proteasome inhibition on lipopolysaccharide-induced signaling events. J Immunol. 2003 Aug 1;171(3):1515-25. PMID:12874245
  9. ↑ Martinez-Solano L, Reales-Calderon JA, Nombela C, Molero G, Gil C. Proteomics of RAW 264.7 macrophages upon interaction with heat-inactivated Candida albicans cells unravel an anti-inflammatory response. Proteomics. 2009 Jun;9(11):2995-3010. doi: 10.1002/pmic.200800016. PMID:19526544 doi:http://dx.doi.org/10.1002/pmic.200800016
  10. ↑ Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell. 2012 Feb 17;148(4):727-38. PMID:22341445 doi:10.1016/j.cell.2011.12.030

3unh, resolution 3.20Å

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