CRL2(ZER1/ZYG11B) recognizes small N-terminal residues for degradation.
CRL2(ZER1/ZYG11B) recognizes small N-terminal residues for degradation.
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CRL2ZER1/ZYG11B 识别小的 N 端残基进行降解
DOI：
10.1038/s41467-022-35169-6
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发表时间：
2022-12-10
影响因子：
16.6
通讯作者：
Mi, Wenyi
中科院分区：
文献类型：
--
作者：
Li, Yao;Zhao, Yueling;Yan, Xiaojie;Ye, Chen;Weirich, Sara;Zhang, Bing;Wang, Xiaolu;Song, Lili;Jiang, Chenhao;Jeltsch, Albert;Dong, Cheng;Mi, Wenyi
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. N-degron pathways play an important role in maintaining protein homeostasis. Here, Li et al. demonstrates an additional non-Ac/N-degron pathway, in which N-terminal non-acetylated small residue degrons (Ser, Ala, or Cys) are recognized by CRL2ZER1/ZYG11B and targeted for protein degradation.
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DOI：
10.1073/pnas.1718336115
发表时间：
2018-04-24
影响因子：
11.1
作者：
Drazic A;Aksnes H;Marie M;Boczkowska M;Varland S;Timmerman E;Foyn H;Glomnes N;Rebowski G;Impens F;Gevaert K;Dominguez R;Arnesen T
通讯作者：
Arnesen T
影响因子：
16.8
作者：
Choi, Woo Suk;Jeong, Byung-Cheon;Song, Hyun Kyu
通讯作者：
Song, Hyun Kyu
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444902016657
发表时间：
2002-11-01
影响因子：
2.2
作者：
Adams, PD;Grosse-Kunstleve, RW;Terwilliger, TC
通讯作者：
Terwilliger, TC
DOI：
10.1073/pnas.2007085117
发表时间：
2020-06-23
影响因子：
11.1
作者：
Dong, Cheng;Chen, Shun-Jia;Min, Jinrong
通讯作者：
Min, Jinrong