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| | ==ER Aminopeptidase, ERAP1, Bound to the Zinc Aminopeptidase Inhibitor, Bestatin== | | ==ER Aminopeptidase, ERAP1, Bound to the Zinc Aminopeptidase Inhibitor, Bestatin== |
| - | <StructureSection load='3mdj' size='340' side='right' caption='[[3mdj]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='3mdj' size='340' side='right'caption='[[3mdj]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mdj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mdj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MDJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERAP1, APPILS, ARTS1, KIAA0525, UNQ584/PRO1154 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERAP1, APPILS, ARTS1, KIAA0525, UNQ584/PRO1154 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mdj OCA], [http://pdbe.org/3mdj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mdj RCSB], [http://www.ebi.ac.uk/pdbsum/3mdj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mdj ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mdj OCA], [https://pdbe.org/3mdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mdj RCSB], [https://www.ebi.ac.uk/pdbsum/3mdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mdj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ERAP1_HUMAN ERAP1_HUMAN]] Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney.<ref>PMID:15908954</ref> <ref>PMID:16286653</ref> <ref>PMID:21478864</ref> | + | [[https://www.uniprot.org/uniprot/ERAP1_HUMAN ERAP1_HUMAN]] Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney.<ref>PMID:15908954</ref> <ref>PMID:16286653</ref> <ref>PMID:21478864</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3mdj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3mdj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Nguyen, T T]] | | [[Category: Nguyen, T T]] |
| | [[Category: Stern, L J]] | | [[Category: Stern, L J]] |
| Structural highlights
3mdj is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , |
| Gene: | ERAP1, APPILS, ARTS1, KIAA0525, UNQ584/PRO1154 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ERAP1_HUMAN] Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney.[1] [2] [3]
Publication Abstract from PubMed
ERAP1 trims antigen precursors to fit into MHC class I proteins. To fulfill this function, ERAP1 has unique substrate preferences, trimming long peptides but sparing shorter ones. To identify the structural basis for ERAP1's unusual properties, we determined the X-ray crystal structure of human ERAP1 bound to bestatin. The structure reveals an open conformation with a large interior compartment. An extended groove originating from the enzyme's catalytic center can accommodate long peptides and has features that explain ERAP1's broad specificity for antigenic peptide precursors. Structural and biochemical analyses suggest a mechanism for ERAP1's length-dependent trimming activity, whereby binding of long rather than short substrates induces a conformational change with reorientation of a key catalytic residue toward the active site. ERAP1's unique structural elements suggest how a generic aminopeptidase structure has been adapted for the specialized function of trimming antigenic precursors.
Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1.,Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ Nat Struct Mol Biol. 2011 May;18(5):604-13. Epub 2011 Apr 10. PMID:21478864[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, Greer F, Schomburg L, Fruci D, Niedermann G, van Endert PM. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol. 2005 Jul;6(7):689-97. Epub 2005 May 22. PMID:15908954 doi:http://dx.doi.org/10.1038/ni1208
- ↑ Chang SC, Momburg F, Bhutani N, Goldberg AL. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17107-12. Epub 2005 Nov 14. PMID:16286653 doi:http://dx.doi.org/0500721102
- ↑ Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol. 2011 May;18(5):604-13. Epub 2011 Apr 10. PMID:21478864 doi:10.1038/nsmb.2021
- ↑ Nguyen TT, Chang SC, Evnouchidou I, York IA, Zikos C, Rock KL, Goldberg AL, Stratikos E, Stern LJ. Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1. Nat Struct Mol Biol. 2011 May;18(5):604-13. Epub 2011 Apr 10. PMID:21478864 doi:10.1038/nsmb.2021
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