3se6: Difference between revisions

Latest revision as of 02:23, 21 November 2024

Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2

Structural highlights

3se6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.08Å
Ligands:	LYS, MAN, MES, NAG, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ERAP2_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. Preferentially hydrolyzes the basic residues Arg and Lys.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 cooperate to trim a vast variety of antigenic peptide precursors to generate mature epitopes for binding to major histocompatibility class I molecules. We report here the first structure of ERAP2 determined at 3.08 A by X-ray crystallography. On the basis of residual electron density, a lysine residue has been modeled in the active site of the enzyme; thus, the structure corresponds to an enzyme-product complex. The overall domain organization is highly similar to that of the recently determined structure of ERAP1 in its closed conformation. A large internal cavity adjacent to the catalytic site can accommodate large peptide substrates. The ERAP2 structure provides a structural explanation for the different peptide N-terminal specificities between ERAP1 and ERAP2 and suggests that such differences extend throughout the whole peptide sequence. A noncrystallographic dimer observed may constitute a model for a proposed ERAP1-ERAP2 heterodimer. Overall, the structure helps explain how two homologous aminopeptidases cooperate to process a large variety of sequences, a key property of their biological role.

The Crystal Structure of Human Endoplasmic Reticulum Aminopeptidase 2 Reveals the Atomic Basis for Distinct Roles in Antigen Processing.,Birtley JR, Saridakis E, Stratikos E, Mavridis IM Biochemistry. 2011 Dec 9. PMID:22106953^[4]

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

References

↑ Tanioka T, Hattori A, Masuda S, Nomura Y, Nakayama H, Mizutani S, Tsujimoto M. Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. J Biol Chem. 2003 Aug 22;278(34):32275-83. Epub 2003 Jun 10. PMID:12799365 doi:https://dx.doi.org/10.1074/jbc.M305076200
↑ 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:https://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:https://dx.doi.org/0500721102
↑ Birtley JR, Saridakis E, Stratikos E, Mavridis IM. The Crystal Structure of Human Endoplasmic Reticulum Aminopeptidase 2 Reveals the Atomic Basis for Distinct Roles in Antigen Processing. Biochemistry. 2011 Dec 9. PMID:22106953 doi:10.1021/bi201230p

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OCA

[1] Tanioka T, Hattori A, Masuda S, Nomura Y, Nakayama H, Mizutani S, Tsujimoto M. Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. J Biol Chem. 2003 Aug 22;278(34):32275-83. Epub 2003 Jun 10. PMID:12799365 doi:https://dx.doi.org/10.1074/jbc.M305076200

[2] 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:https://dx.doi.org/10.1038/ni1208

[3] 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:https://dx.doi.org/0500721102

[4] Birtley JR, Saridakis E, Stratikos E, Mavridis IM. The Crystal Structure of Human Endoplasmic Reticulum Aminopeptidase 2 Reveals the Atomic Basis for Distinct Roles in Antigen Processing. Biochemistry. 2011 Dec 9. PMID:22106953 doi:10.1021/bi201230p

[1]

[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='3se6' size='340' side='right'caption='[[3se6]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3se6]] is a 2 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=3SE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SE6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3se6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SE6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.08&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERAP2, LRAP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3se6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3se6 OCA], [https://pdbe.org/3se6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3se6 RCSB], [https://www.ebi.ac.uk/pdbsum/3se6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3se6 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/ERAP2_HUMAN ERAP2_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. Preferentially hydrolyzes the basic residues Arg and Lys.<ref>PMID:12799365</ref> <ref>PMID:15908954</ref> <ref>PMID:16286653</ref>
+[https://www.uniprot.org/uniprot/ERAP2_HUMAN ERAP2_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. Preferentially hydrolyzes the basic residues Arg and Lys.<ref>PMID:12799365</ref> <ref>PMID:15908954</ref> <ref>PMID:16286653</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Birtley, J R]]
+[[Category: Birtley JR]]
-[[Category: Mavridis, I M]]
+[[Category: Mavridis IM]]
-[[Category: Saridakis, E]]
+[[Category: Saridakis E]]
-[[Category: Stratikos, E]]
+[[Category: Stratikos E]]
-[[Category: Aminopeptidase]]
-[[Category: Endoplasmic reticulum]]
-[[Category: Glycosylation]]
-[[Category: Hydrolase]]
-[[Category: Thermolysin-like catalytic domain]]
-[[Category: Zinc binding]]

3se6: Difference between revisions

Latest revision as of 02:23, 21 November 2024

Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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