6klr

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human WIPI3 in complex with the WIR-peptide from ATG2A

Structural highlights

6klr 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 2.21Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

WIPI3_HUMAN The disease may be caused by mutations affecting the gene represented in this entry.

Function

ATG2A_HUMAN Involved in autophagosome assembly, regulating the size of nascent autophagosomes (PubMed:28561066). Also regulates lipid droplets morphology and distribution within the cell (PubMed:22219374, PubMed:28561066).^[1] ^[2] WIPI3_HUMAN Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2 (PubMed:28561066). In the cellular response to starvation, may also function together with the TSC1-TSC2 complex and RB1CC1 in the inhibition of the mTORC1 signaling pathway (PubMed:28503735).^[3] ^[4]

Publication Abstract from PubMed

WIPI proteins (WIPI1-4) are mammalian PROPPIN family phosphoinositide effectors essential for autophagosome biogenesis. In addition to phosphoinositides, WIPI proteins can recognize a linear WIPI-interacting-region (WIR)-motif, but the underlying mechanism is poorly understood. Here, we determine the structure of WIPI3 in complex with the WIR-peptide from ATG2A. Unexpectedly, the WIR-peptide entwines around the WIPI3 seven-bladed beta-propeller and binds to three sites in blades 1-3. The N-terminal part of the WIR-peptide forms a short strand that augments the periphery of blade 2, the middle segment anchors into an inter-blade hydrophobic pocket between blades 2-3, and the C-terminal aromatic tail wedges into another tailored pocket between blades 1-2. Mutations in three peptide-binding sites disrupt the interactions between WIPI3/4 and ATG2A and impair the ATG2A-mediated autophagic process. Thus, WIPI proteins recognize the WIR-motif by multi-sites in multi-blades and this multi-site-mediated peptide-recognition mechanism could be applicable to other PROPPIN proteins.

Multi-site-mediated entwining of the linear WIR-motif around WIPI beta-propellers for autophagy.,Ren J, Liang R, Wang W, Zhang D, Yu L, Feng W Nat Commun. 2020 Jun 1;11(1):2702. doi: 10.1038/s41467-020-16523-y. PMID:32483132^[5]

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

References

↑ Velikkakath AK, Nishimura T, Oita E, Ishihara N, Mizushima N. Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol Biol Cell. 2012 Mar;23(5):896-909. doi: 10.1091/mbc.E11-09-0785. Epub 2012, Jan 4. PMID:22219374 doi:http://dx.doi.org/10.1091/mbc.E11-09-0785
↑ Bakula D, Muller AJ, Zuleger T, Takacs Z, Franz-Wachtel M, Thost AK, Brigger D, Tschan MP, Frickey T, Robenek H, Macek B, Proikas-Cezanne T. WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nat Commun. 2017 May 31;8:15637. doi: 10.1038/ncomms15637. PMID:28561066 doi:http://dx.doi.org/10.1038/ncomms15637
↑ Suleiman J, Allingham-Hawkins D, Hashem M, Shamseldin HE, Alkuraya FS, El-Hattab AW. WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome. Clin Genet. 2018 Feb;93(2):360-364. doi: 10.1111/cge.13054. Epub 2017 Sep 7. PMID:28503735 doi:http://dx.doi.org/10.1111/cge.13054
↑ Bakula D, Muller AJ, Zuleger T, Takacs Z, Franz-Wachtel M, Thost AK, Brigger D, Tschan MP, Frickey T, Robenek H, Macek B, Proikas-Cezanne T. WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nat Commun. 2017 May 31;8:15637. doi: 10.1038/ncomms15637. PMID:28561066 doi:http://dx.doi.org/10.1038/ncomms15637
↑ Ren J, Liang R, Wang W, Zhang D, Yu L, Feng W. Multi-site-mediated entwining of the linear WIR-motif around WIPI beta-propellers for autophagy. Nat Commun. 2020 Jun 1;11(1):2702. doi: 10.1038/s41467-020-16523-y. PMID:32483132 doi:http://dx.doi.org/10.1038/s41467-020-16523-y

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6klr"

Categories: Homo sapiens | Large Structures | Feng W | Liang RB | Ren JQ

@@ Line 3: / Line 3: @@
 <StructureSection load='6klr' size='340' side='right'caption='[[6klr]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6klr]] is a 2 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=6KLR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KLR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6klr]] 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=6KLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KLR FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WDR45B, WDR45L, WIPI3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.21&#8491;</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=6klr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6klr OCA], [http://pdbe.org/6klr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6klr RCSB], [http://www.ebi.ac.uk/pdbsum/6klr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6klr 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=6klr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6klr OCA], [https://pdbe.org/6klr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6klr RCSB], [https://www.ebi.ac.uk/pdbsum/6klr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6klr ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/WIPI3_HUMAN WIPI3_HUMAN] The disease may be caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/ATG2A_HUMAN ATG2A_HUMAN]] Involved in autophagosome assembly, regulating the size of nascent autophagosomes (PubMed:28561066). Also regulates lipid droplets morphology and distribution within the cell (PubMed:22219374, PubMed:28561066).<ref>PMID:22219374</ref> <ref>PMID:28561066</ref>
+[https://www.uniprot.org/uniprot/ATG2A_HUMAN ATG2A_HUMAN] Involved in autophagosome assembly, regulating the size of nascent autophagosomes (PubMed:28561066). Also regulates lipid droplets morphology and distribution within the cell (PubMed:22219374, PubMed:28561066).<ref>PMID:22219374</ref> <ref>PMID:28561066</ref> [https://www.uniprot.org/uniprot/WIPI3_HUMAN WIPI3_HUMAN] Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2 (PubMed:28561066). In the cellular response to starvation, may also function together with the TSC1-TSC2 complex and RB1CC1 in the inhibition of the mTORC1 signaling pathway (PubMed:28503735).<ref>PMID:28503735</ref> <ref>PMID:28561066</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Feng, W]]
+[[Category: Feng W]]
-[[Category: Liang, R B]]
+[[Category: Liang RB]]
-[[Category: Ren, J Q]]
+[[Category: Ren JQ]]
-[[Category: Lipid binding protein]]
-[[Category: Membrane bound protein]]

6klr

From Proteopedia

Current revision

Crystal structure of human WIPI3 in complex with the WIR-peptide from ATG2A

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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