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5gu6

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Revision as of 06:43, 20 May 2020

Crystal structure of Human ERp44 form I

Structural highlights

5gu6 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5gu7
Gene:	ERP44, KIAA0573, TXNDC4, UNQ532/PRO1075 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ERP44_HUMAN] Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1L and ERO1LB in the endoplasmic reticulum.^[1] ^[2]

Publication Abstract from PubMed

ERp44 retrieves some endoplasmic reticulum (ER)-resident enzymes and immature oligomers of secretory proteins from the Golgi. Association of ERp44 with its clients is regulated by pH-dependent mechanisms, but the molecular details are not fully understood. Here we report high-resolution crystal structures of human ERp44 at neutral and weakly acidic pH. These structures reveal key regions in the C-terminal tail (C tail) missing in the original crystal structure, including a regulatory histidine-rich region and a subsequent extended loop. The former region forms a short alpha-helix (alpha16), generating a histidine-clustered site (His cluster). At low pH, the three Trx-like domains of ERp44 ("a," "b," and "b'") undergo significant rearrangements, likely induced by protonation of His157 located at the interface between the a and b domains. The alpha16-helix is partially unwound and the extended loop is disordered in weakly acidic conditions, probably due to electrostatic repulsion between the protonated histidines in the His cluster. Molecular dynamics simulations indicated that helix unwinding enhances the flexibility of the C tail, disrupting its normal hydrogen-bonding pattern. The observed pH-dependent conformational changes significantly enlarge the positively charged regions around the client-binding site of ERp44 at low pH. Mutational analyses showed that ERp44 forms mixed disulfides with specific cysteines residing on negatively charged loop regions of Ero1alpha. We propose that the protonation states of the essential histidines regulate the ERp44-client interaction by altering the C-tail dynamics and surface electrostatic potential of ERp44.

Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface.,Watanabe S, Harayama M, Kanemura S, Sitia R, Inaba K Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3224-E3232. doi:, 10.1073/pnas.1621426114. Epub 2017 Apr 3. PMID:28373561^[3]

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

References

↑ Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, Sitia R. ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 2002 Feb 15;21(4):835-44. PMID:11847130 doi:http://dx.doi.org/10.1093/emboj/21.4.835
↑ Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, Mezghrani A, Ruffato E, Simmen T, Sitia R. Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J. 2003 Oct 1;22(19):5015-22. PMID:14517240 doi:http://dx.doi.org/10.1093/emboj/cdg491
↑ Watanabe S, Harayama M, Kanemura S, Sitia R, Inaba K. Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface. Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3224-E3232. doi:, 10.1073/pnas.1621426114. Epub 2017 Apr 3. PMID:28373561 doi:http://dx.doi.org/10.1073/pnas.1621426114

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5gu6"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Human ERp44 form I==
-<StructureSection load='5gu6' size='340' side='right' caption='[[5gu6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5gu6' size='340' side='right'caption='[[5gu6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5gu6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GU6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5gu6]] is a 1 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=5GU6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GU6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gu7|5gu7]]</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=5gu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gu6 OCA], [http://pdbe.org/5gu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gu6 RCSB], [http://www.ebi.ac.uk/pdbsum/5gu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gu6 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERP44, KIAA0573, TXNDC4, UNQ532/PRO1075 ([http://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://proteopedia.org/fgij/fg.htm?mol=5gu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gu6 OCA], [http://pdbe.org/5gu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gu6 RCSB], [http://www.ebi.ac.uk/pdbsum/5gu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gu6 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5gu6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[ER-resident protein|ER-resident protein]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Inaba, K]]
 [[Category: Watanabe, S]]
 [[Category: Chaperone]]
 [[Category: Quality control]]

5gu6

From Proteopedia

Revision as of 06:43, 20 May 2020

Crystal structure of Human ERp44 form I

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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