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CRL2ZER1/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 13 7636 (2022)
Related entries: 7xys, 7xyt, 7xyv, 7xyw, 7xyx

Cited: 4 times
EuropePMC logo PMID: 36496439

Abstract

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.

Articles - 7xyu mentioned but not cited (1)

  1. CRL2ZER1/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 13 7636 (2022)


Articles citing this publication (3)

  1. Recognition of an Ala-rich C-degron by the E3 ligase Pirh2. Wang X, Li Y, Yan X, Yang Q, Zhang B, Zhang Y, Yuan X, Jiang C, Chen D, Liu Q, Liu T, Mi W, Yu Y, Dong C. Nat Commun 14 2474 (2023)
  2. N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity. Varland S, Silva RD, Kjosås I, Faustino A, Bogaert A, Billmann M, Boukhatmi H, Kellen B, Costanzo M, Drazic A, Osberg C, Chan K, Zhang X, Tong AHY, Andreazza S, Lee JJ, Nedyalkova L, Ušaj M, Whitworth AJ, Andrews BJ, Moffat J, Myers CL, Gevaert K, Boone C, Martinho RG, Arnesen T. Nat Commun 14 6774 (2023)
  3. NatB Catalytic Subunit Depletion Disrupts DNA Replication Initiation Leading to Senescence in MEFs. Elurbide J, Carte B, Guedes J, Aldabe R. Int J Mol Sci 24 8724 (2023)


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