8x8k

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of STBD1 CBM20 domain in complex with maltotetraose

Structural highlights

8x8k is a 4 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 2.1Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

STBD1_HUMAN Acts as a cargo receptor for glycogen. Delivers its cargo to an autophagic pathway called glycophagy, resulting in the transport of glycogen to lysosomes.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Autophagy of glycogen (glycophagy) is crucial for the maintenance of cellular glucose homeostasis and physiology in mammals. STBD1 can serve as an autophagy receptor to mediate glycophagy by specifically recognizing glycogen and relevant key autophagic factors, but with poorly understood mechanisms. Here, we systematically characterize the interactions of STBD1 with glycogen and related saccharides, and determine the crystal structure of the STBD1 CBM20 domain with maltotetraose, uncovering a unique binding mode involving two different oligosaccharide-binding sites adopted by STBD1 CBM20 for recognizing glycogen. In addition, we demonstrate that the LC3-interacting region (LIR) motif of STBD1 can selectively bind to six mammalian ATG8 family members. We elucidate the detailed molecular mechanism underlying the selective interactions of STBD1 with ATG8 family proteins by solving the STBD1 LIR/GABARAPL1 complex structure. Importantly, our cell-based assays reveal that both the STBD1 LIR/GABARAPL1 interaction and the intact two oligosaccharide binding sites of STBD1 CBM20 are essential for the effective association of STBD1, GABARAPL1, and glycogen in cells. Finally, through mass spectrometry, biochemical, and structural modeling analyses, we unveil that STBD1 can directly bind to the Claw domain of RB1CC1 through its LIR, thereby recruiting the key autophagy initiation factor RB1CC1. In all, our findings provide mechanistic insights into the recognitions of glycogen, ATG8 family proteins, and RB1CC1 by STBD1 and shed light on the potential working mechanism of STBD1-mediated glycophagy.

Decoding the molecular mechanism of selective autophagy of glycogen mediated by autophagy receptor STBD1.,Zhang Y, Sun Y, Shi J, Xu P, Wang Y, Liu J, Gong X, Wang Y, Tang Y, Liu H, Zhou X, Lin Z, Baba O, Morita T, Yu B, Pan L Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2402817121. doi: , 10.1073/pnas.2402817121. Epub 2024 Sep 5. PMID:39236246^[4]

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

References

↑ Jiang S, Heller B, Tagliabracci VS, Zhai L, Irimia JM, DePaoli-Roach AA, Wells CD, Skurat AV, Roach PJ. Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism. J Biol Chem. 2010 Nov 5;285(45):34960-71. PMID:20810658 doi:10.1074/jbc.M110.150839
↑ Jiang S, Wells CD, Roach PJ. Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1. Biochem Biophys Res Commun. 2011 Sep 30;413(3):420-5. PMID:21893048 doi:10.1016/j.bbrc.2011.08.106
↑ Zhu Y, Zhang M, Kelly AR, Cheng A. The carbohydrate-binding domain of overexpressed STBD1 is important for its stability and protein-protein interactions. Biosci Rep. 2014 Jul 1;34(4):e00117. PMID:24837458 doi:10.1042/BSR20140053
↑ Zhang Y, Sun Y, Shi J, Xu P, Wang Y, Liu J, Gong X, Wang Y, Tang Y, Liu H, Zhou X, Lin Z, Baba O, Morita T, Yu B, Pan L. Decoding the molecular mechanism of selective autophagy of glycogen mediated by autophagy receptor STBD1. Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2402817121. PMID:39236246 doi:10.1073/pnas.2402817121

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8x8k"

Categories: Homo sapiens | Large Structures | Pan LF | Zhang YC

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8x8k is ON HOLD  until Paper Publication
+==Crystal structure of STBD1 CBM20 domain in complex with maltotetraose==
+<StructureSection load='8x8k' size='340' side='right'caption='[[8x8k]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8x8k]] is a 4 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=8X8K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8X8K FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PRD_900010:alpha-maltotetraose'>PRD_900010</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=8x8k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8x8k OCA], [https://pdbe.org/8x8k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8x8k RCSB], [https://www.ebi.ac.uk/pdbsum/8x8k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8x8k ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/STBD1_HUMAN STBD1_HUMAN] Acts as a cargo receptor for glycogen. Delivers its cargo to an autophagic pathway called glycophagy, resulting in the transport of glycogen to lysosomes.<ref>PMID:20810658</ref> <ref>PMID:21893048</ref> <ref>PMID:24837458</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Autophagy of glycogen (glycophagy) is crucial for the maintenance of cellular glucose homeostasis and physiology in mammals. STBD1 can serve as an autophagy receptor to mediate glycophagy by specifically recognizing glycogen and relevant key autophagic factors, but with poorly understood mechanisms. Here, we systematically characterize the interactions of STBD1 with glycogen and related saccharides, and determine the crystal structure of the STBD1 CBM20 domain with maltotetraose, uncovering a unique binding mode involving two different oligosaccharide-binding sites adopted by STBD1 CBM20 for recognizing glycogen. In addition, we demonstrate that the LC3-interacting region (LIR) motif of STBD1 can selectively bind to six mammalian ATG8 family members. We elucidate the detailed molecular mechanism underlying the selective interactions of STBD1 with ATG8 family proteins by solving the STBD1 LIR/GABARAPL1 complex structure. Importantly, our cell-based assays reveal that both the STBD1 LIR/GABARAPL1 interaction and the intact two oligosaccharide binding sites of STBD1 CBM20 are essential for the effective association of STBD1, GABARAPL1, and glycogen in cells. Finally, through mass spectrometry, biochemical, and structural modeling analyses, we unveil that STBD1 can directly bind to the Claw domain of RB1CC1 through its LIR, thereby recruiting the key autophagy initiation factor RB1CC1. In all, our findings provide mechanistic insights into the recognitions of glycogen, ATG8 family proteins, and RB1CC1 by STBD1 and shed light on the potential working mechanism of STBD1-mediated glycophagy.
-Authors:
+Decoding the molecular mechanism of selective autophagy of glycogen mediated by autophagy receptor STBD1.,Zhang Y, Sun Y, Shi J, Xu P, Wang Y, Liu J, Gong X, Wang Y, Tang Y, Liu H, Zhou X, Lin Z, Baba O, Morita T, Yu B, Pan L Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2402817121. doi: , 10.1073/pnas.2402817121. Epub 2024 Sep 5. PMID:39236246<ref>PMID:39236246</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8x8k" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Pan LF]]
+[[Category: Zhang YC]]

8x8k

From Proteopedia

Current revision

Crystal structure of STBD1 CBM20 domain in complex with maltotetraose

Structural highlights

Function

Publication Abstract from PubMed

References

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