7ep2

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of ZYG11B bound to GGFN degron

Structural highlights

7ep2 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 2.38Å
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 pathways are a set of proteolytic systems that target the N-terminal destabilizing residues of substrates for proteasomal degradation. Recently, the Gly/N-degron pathway has been identified as a new branch of the N-degron pathway. The N-terminal glycine degron (Gly/N-degron) is recognized by ZYG11B and ZER1, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we present the crystal structures of ZYG11B and ZER1 bound to various Gly/N-degrons. The structures reveal that ZYG11B and ZER1 utilize their armadillo (ARM) repeats forming a deep and narrow cavity to engage mainly the first four residues of Gly/N-degrons. The alpha-amino group of the Gly/N-degron is accommodated in an acidic pocket by five conserved hydrogen bonds. These structures, together with biochemical studies, decipher the molecular basis for the specific recognition of the Gly/N-degron by ZYG11B and ZER1, providing key information for future structure-based chemical probe design.

Molecular basis for recognition of Gly/N-degrons by CRL2(ZYG11B) and CRL2(ZER1).,Yan X, Li Y, Wang G, Zhou Z, Song G, Feng Q, Zhao Y, Mi W, Ma Z, Dong C Mol Cell. 2021 Jun 23. pii: S1097-2765(21)00457-3. doi:, 10.1016/j.molcel.2021.06.010. PMID:34214466^[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
↑ Yan X, Li Y, Wang G, Zhou Z, Song G, Feng Q, Zhao Y, Mi W, Ma Z, Dong C. Molecular basis for recognition of Gly/N-degrons by CRL2(ZYG11B) and CRL2(ZER1). Mol Cell. 2021 Aug 19;81(16):3262-3274.e3. PMID:34214466 doi:10.1016/j.molcel.2021.06.010

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/7ep2"

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

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7ep2 is ON HOLD  until Paper Publication
+==Crystal structure of ZYG11B bound to GGFN degron==
+<StructureSection load='7ep2' size='340' side='right'caption='[[7ep2]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7ep2]] 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=7EP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EP2 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]] 2.38&#8491;</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=7ep2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ep2 OCA], [https://pdbe.org/7ep2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ep2 RCSB], [https://www.ebi.ac.uk/pdbsum/7ep2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ep2 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 pathways are a set of proteolytic systems that target the N-terminal destabilizing residues of substrates for proteasomal degradation. Recently, the Gly/N-degron pathway has been identified as a new branch of the N-degron pathway. The N-terminal glycine degron (Gly/N-degron) is recognized by ZYG11B and ZER1, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we present the crystal structures of ZYG11B and ZER1 bound to various Gly/N-degrons. The structures reveal that ZYG11B and ZER1 utilize their armadillo (ARM) repeats forming a deep and narrow cavity to engage mainly the first four residues of Gly/N-degrons. The alpha-amino group of the Gly/N-degron is accommodated in an acidic pocket by five conserved hydrogen bonds. These structures, together with biochemical studies, decipher the molecular basis for the specific recognition of the Gly/N-degron by ZYG11B and ZER1, providing key information for future structure-based chemical probe design.
-Authors:
+Molecular basis for recognition of Gly/N-degrons by CRL2(ZYG11B) and CRL2(ZER1).,Yan X, Li Y, Wang G, Zhou Z, Song G, Feng Q, Zhao Y, Mi W, Ma Z, Dong C Mol Cell. 2021 Jun 23. pii: S1097-2765(21)00457-3. doi:, 10.1016/j.molcel.2021.06.010. PMID:34214466<ref>PMID:34214466</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 7ep2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Li Y]]
+[[Category: Yan X]]

7ep2

From Proteopedia

Current revision

Crystal structure of ZYG11B bound to GGFN degron

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox