7xyv

From Proteopedia

(Difference between revisions)

Revision as of 09:25, 21 December 2022

Crystal structure of ZYG11B bound to SFLH degron

Structural highlights

7xyv 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.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ZY11B_HUMAN Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC. Acts redudantly with ZER1 to target substrates bearing N-terminal glycine degrons for proteasomal degradation (PubMed:33093214). Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N-terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N-myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation (PubMed:31273098).^[1] ^[2]

Publication Abstract from PubMed

N-degron pathway plays an important role in the protein quality control and maintenance of cellular protein homeostasis. ZER1 and ZYG11B, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2), recognize N-terminal (Nt) glycine degrons and participate in the Nt-myristoylation quality control through the Gly/N-degron pathway. Here we show that ZER1 and ZYG11B can also recognize small Nt-residues other than glycine. Specifically, ZER1 binds better to Nt-Ser, -Ala, -Thr and -Cys than to -Gly, while ZYG11B prefers Nt-Gly but also has the capacity to recognize Nt-Ser, -Ala and -Cys in vitro. We found that Nt-Ser, -Ala and -Cys undergo Nt-acetylation catalyzed by Nt-acetyltransferase (NAT), thereby shielding them from recognition by ZER1/ZYG11B in cells. Instead, ZER1/ZYG11B readily targets a selection of small Nt-residues lacking Nt-acetylation for degradation in NAT-deficient cells, implicating its role in the Nt-acetylation quality control. Furthermore, we present the crystal structures of ZER1 and ZYG11B bound to various small Nt-residues and uncover the molecular mechanism of non-acetylated substrate recognition by ZER1 and ZYG11B.

CRL2(ZER1/ZYG11B) recognizes small N-terminal residues for degradation.,Li Y, Zhao Y, Yan X, Ye C, Weirich S, Zhang B, Wang X, Song L, Jiang C, Jeltsch A, Dong C, Mi W Nat Commun. 2022 Dec 10;13(1):7636. doi: 10.1038/s41467-022-35169-6. PMID:36496439^[3]

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

References

↑ Timms RT, Zhang Z, Rhee DY, Harper JW, Koren I, Elledge SJ. A glycine-specific N-degron pathway mediates the quality control of protein N-myristoylation. Science. 2019 Jul 5;365(6448):eaaw4912. doi: 10.1126/science.aaw4912. PMID:31273098 doi:http://dx.doi.org/10.1126/science.aaw4912
↑ Robinson KS, Teo DET, Tan KS, Toh GA, Ong HH, Lim CK, Lay K, Au BV, Lew TS, Chu JJH, Chow VTK, Wang Y, Zhong FL, Reversade B. Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia. Science. 2020 Dec 4;370(6521):eaay2002. doi: 10.1126/science.aay2002. Epub 2020 , Oct 22. PMID:33093214 doi:http://dx.doi.org/10.1126/science.aay2002
↑ Li Y, Zhao Y, Yan X, Ye C, Weirich S, Zhang B, Wang X, Song L, Jiang C, Jeltsch A, Dong C, Mi W. CRL2(ZER1/ZYG11B) recognizes small N-terminal residues for degradation. Nat Commun. 2022 Dec 10;13(1):7636. doi: 10.1038/s41467-022-35169-6. PMID:36496439 doi:http://dx.doi.org/10.1038/s41467-022-35169-6

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/7xyv"

Categories: Homo sapiens | Large Structures | Dong C | Li Y | Yan X

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7xyv is ON HOLD  until Paper Publication
+==Crystal structure of ZYG11B bound to SFLH degron==
+<StructureSection load='7xyv' size='340' side='right'caption='[[7xyv]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7xyv]] 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=7XYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XYV 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=7xyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xyv OCA], [https://pdbe.org/7xyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xyv RCSB], [https://www.ebi.ac.uk/pdbsum/7xyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xyv ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ZY11B_HUMAN ZY11B_HUMAN] Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC. Acts redudantly with ZER1 to target substrates bearing N-terminal glycine degrons for proteasomal degradation (PubMed:33093214). Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N-terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N-myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation (PubMed:31273098).<ref>PMID:31273098</ref> <ref>PMID:33093214</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+N-degron pathway plays an important role in the protein quality control and maintenance of cellular protein homeostasis. ZER1 and ZYG11B, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2), recognize N-terminal (Nt) glycine degrons and participate in the Nt-myristoylation quality control through the Gly/N-degron pathway. Here we show that ZER1 and ZYG11B can also recognize small Nt-residues other than glycine. Specifically, ZER1 binds better to Nt-Ser, -Ala, -Thr and -Cys than to -Gly, while ZYG11B prefers Nt-Gly but also has the capacity to recognize Nt-Ser, -Ala and -Cys in vitro. We found that Nt-Ser, -Ala and -Cys undergo Nt-acetylation catalyzed by Nt-acetyltransferase (NAT), thereby shielding them from recognition by ZER1/ZYG11B in cells. Instead, ZER1/ZYG11B readily targets a selection of small Nt-residues lacking Nt-acetylation for degradation in NAT-deficient cells, implicating its role in the Nt-acetylation quality control. Furthermore, we present the crystal structures of ZER1 and ZYG11B bound to various small Nt-residues and uncover the molecular mechanism of non-acetylated substrate recognition by ZER1 and ZYG11B.
-Authors: Dong, C., Yan, X., Li, Y.
+CRL2(ZER1/ZYG11B) recognizes small N-terminal residues for degradation.,Li Y, Zhao Y, Yan X, Ye C, Weirich S, Zhang B, Wang X, Song L, Jiang C, Jeltsch A, Dong C, Mi W Nat Commun. 2022 Dec 10;13(1):7636. doi: 10.1038/s41467-022-35169-6. PMID:36496439<ref>PMID:36496439</ref>
-Description: Crystal structure of ZYG11B bound to ORF10 peptide
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Yan, X]]
+<div class="pdbe-citations 7xyv" style="background-color:#fffaf0;"></div>
-[[Category: Dong, C]]
+== References ==
-[[Category: Li, Y]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Dong C]]
+[[Category: Li Y]]
+[[Category: Yan X]]

7xyv

From Proteopedia

Revision as of 09:25, 21 December 2022

Crystal structure of ZYG11B bound to SFLH degron

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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