6zay

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Atg16L in complex with GDP-bound Rab33B

Structural highlights

6zay is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RB33B_HUMAN Smith-McCort dysplasia. The disease is caused by variants affecting the gene represented in this entry.

Function

RB33B_HUMAN Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking. It is involved in autophagy, acting as a modulator of autophagosome formation.^[1]

Publication Abstract from PubMed

Autophagosome formation is a fundamental process in macroautophagy/autophagy, a conserved self-eating mechanism in all eukaryotes, which requires the conjugating ATG (autophagy related) protein complex, ATG12-ATG5-ATG16L1 and lipidated MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). How the ATG12-ATG5-ATG16L1 complex is recruited to membranes is not fully understood. Here, we demonstrated that RAB33B plays a key role in recruiting the ATG16L1 complex to phagophores during starvation-induced autophagy. Crystal structures of RAB33B bound to the coiled-coil domain (CCD) of ATG16L1 revealed the recognition mechanism between RAB33B and ATG16L1. ATG16L1 is a novel RAB-binding protein (RBP) that can induce RAB proteins to adopt active conformation without nucleotide exchange. RAB33B and ATG16L1 mutually determined the localization of each other on phagophores. RAB33B-ATG16L1 interaction was required for LC3 lipidation and autophagosome formation. Upon starvation, a fraction of RAB33B translocated from the Golgi to phagophores and recruited the ATG16L1 complex. In this work, we reported a new mechanism for the recruitment of the ATG12-ATG5-ATG16L1 complex to phagophores by RAB33B, which is required for autophagosome formation. Abbreviations : ATG: autophagy-related; Calpha: alpha carbon; CCD: coiled-coil domain; CLEM: correlative light and electron microscopy; DTE: dithioerythritol; EBSS: Earle's balanced salt solution; EDTA: ethylenediaminetetraacetic acid; EGFP: enhanced green fluorescent protein; FBS: fetal bovine serum; FLIM: fluorescence lifetime imaging microscopy; FRET: Forster resonance energy transfer; GDP: guanosine diphosphate; GOLGA2/GM130: golgin A2; GppNHp: guanosine 5'-[beta,gamma-imido]triphosphate; GST: glutathione S-transferase; GTP: guanosine triphosphate; GTPgammaS: guanosine 5'-O-[gamma-thio]triphosphate; HA (tag): hemagglutinin (tag); HEK: human embryonic kidney; HeLa: Henrietta Lacks; HEPES: (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid); IgG: immunoglobulin G; Kd: dissociation constant; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCF7: Michigan cancer foundation-7; MEF: mouse embryonic fibroblast; MEM: minimum essential medium Eagle; MST: microscale thermophoresis; NEAA: non-essential amino acids; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PtdIns3P: phosphatidylinositol-3-phosphate; RAB: RAS-associated binding; RB1CC1/FIP200: RB1 inducible coiled-coil protein 1; RBP: RAB-binding protein; SD: standard deviation; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; TBS-T: tris-buffered saline-tween 20; WD (repeat): tryptophan-aspartic acid (repeat); WIPI2B: WD repeat domain phosphoinositide interacting 2B; WT: wild type.

RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.,Pantoom S, Konstantinidis G, Voss S, Han H, Hofnagel O, Li Z, Wu YW Autophagy. 2020 Sep 22:1-15. doi: 10.1080/15548627.2020.1822629. PMID:32960676^[2]

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

References

↑ Starr T, Sun Y, Wilkins N, Storrie B. Rab33b and Rab6 are functionally overlapping regulators of Golgi homeostasis and trafficking. Traffic. 2010 May;11(5):626-36. PMID:20163571 doi:10.1111/j.1600-0854.2010.01051.x
↑ Pantoom S, Konstantinidis G, Voss S, Han H, Hofnagel O, Li Z, Wu YW. RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein. Autophagy. 2021 Sep;17(9):2290-2304. PMID:32960676 doi:10.1080/15548627.2020.1822629

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Mus musculus | Pantoom S | Wu YW

@@ Line 1: / Line 1: @@
-====
+==Crystal structure of Atg16L in complex with GDP-bound Rab33B==
-<StructureSection load='6zay' size='340' side='right'caption='[[6zay]]' scene=''>
+<StructureSection load='6zay' size='340' side='right'caption='[[6zay]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6zay]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZAY FirstGlance]. <br>
-</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=6zay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zay OCA], [https://pdbe.org/6zay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zay RCSB], [https://www.ebi.ac.uk/pdbsum/6zay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zay ProSAT]</span></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]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6zay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zay OCA], [https://pdbe.org/6zay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zay RCSB], [https://www.ebi.ac.uk/pdbsum/6zay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zay ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/RB33B_HUMAN RB33B_HUMAN] Smith-McCort dysplasia. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/RB33B_HUMAN RB33B_HUMAN] Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking. It is involved in autophagy, acting as a modulator of autophagosome formation.<ref>PMID:20163571</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Autophagosome formation is a fundamental process in macroautophagy/autophagy, a conserved self-eating mechanism in all eukaryotes, which requires the conjugating ATG (autophagy related) protein complex, ATG12-ATG5-ATG16L1 and lipidated MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). How the ATG12-ATG5-ATG16L1 complex is recruited to membranes is not fully understood. Here, we demonstrated that RAB33B plays a key role in recruiting the ATG16L1 complex to phagophores during starvation-induced autophagy. Crystal structures of RAB33B bound to the coiled-coil domain (CCD) of ATG16L1 revealed the recognition mechanism between RAB33B and ATG16L1. ATG16L1 is a novel RAB-binding protein (RBP) that can induce RAB proteins to adopt active conformation without nucleotide exchange. RAB33B and ATG16L1 mutually determined the localization of each other on phagophores. RAB33B-ATG16L1 interaction was required for LC3 lipidation and autophagosome formation. Upon starvation, a fraction of RAB33B translocated from the Golgi to phagophores and recruited the ATG16L1 complex. In this work, we reported a new mechanism for the recruitment of the ATG12-ATG5-ATG16L1 complex to phagophores by RAB33B, which is required for autophagosome formation. Abbreviations : ATG: autophagy-related; Calpha: alpha carbon; CCD: coiled-coil domain; CLEM: correlative light and electron microscopy; DTE: dithioerythritol; EBSS: Earle's balanced salt solution; EDTA: ethylenediaminetetraacetic acid; EGFP: enhanced green fluorescent protein; FBS: fetal bovine serum; FLIM: fluorescence lifetime imaging microscopy; FRET: Forster resonance energy transfer; GDP: guanosine diphosphate; GOLGA2/GM130: golgin A2; GppNHp: guanosine 5'-[beta,gamma-imido]triphosphate; GST: glutathione S-transferase; GTP: guanosine triphosphate; GTPgammaS: guanosine 5'-O-[gamma-thio]triphosphate; HA (tag): hemagglutinin (tag); HEK: human embryonic kidney; HeLa: Henrietta Lacks; HEPES: (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid); IgG: immunoglobulin G; Kd: dissociation constant; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCF7: Michigan cancer foundation-7; MEF: mouse embryonic fibroblast; MEM: minimum essential medium Eagle; MST: microscale thermophoresis; NEAA: non-essential amino acids; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PtdIns3P: phosphatidylinositol-3-phosphate; RAB: RAS-associated binding; RB1CC1/FIP200: RB1 inducible coiled-coil protein 1; RBP: RAB-binding protein; SD: standard deviation; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; TBS-T: tris-buffered saline-tween 20; WD (repeat): tryptophan-aspartic acid (repeat); WIPI2B: WD repeat domain phosphoinositide interacting 2B; WT: wild type.
+RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.,Pantoom S, Konstantinidis G, Voss S, Han H, Hofnagel O, Li Z, Wu YW Autophagy. 2020 Sep 22:1-15. doi: 10.1080/15548627.2020.1822629. PMID:32960676<ref>PMID:32960676</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6zay" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Autophagy-related protein 3D structures|Autophagy-related protein 3D structures]]
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
+*[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Z-disk]]
+[[Category: Mus musculus]]
+[[Category: Pantoom S]]
+[[Category: Wu YW]]

6zay

From Proteopedia

Current revision

Crystal structure of Atg16L in complex with GDP-bound Rab33B

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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