PXD037312

PXD037312 is an original dataset announced via ProteomeXchange.

Title	CRL2ZER1/ZYG11B recognizes small N-terminal residues for degradation
Description	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 preferentially binds to Nt-serine, -alanine, -threonine and -cysteine over -glycine, while ZYG11B prefers Nt-glycine but also has the capacity to recognize Nt-serine, -alanine and -cysteine in vitro. Nt-serine, -alanine and -cysteine undergo Nt-acetylation by NatA, thereby shielding them from recognition by ZER1/ZYG11B in cells. We found that ZER1/ZYG11B is able to target the non-acetylation of small Nt-residue degrons for degradation in NatA-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 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 preferentially binds to Nt-serine, -alanine, -threonine and -cysteine over -glycine, while ZYG11B prefers Nt-glycine but also has the capacity to recognize Nt-serine, -alanine and -cysteine in vitro. Nt-serine, -alanine and -cysteine undergo Nt-acetylation by NatA, thereby shielding them from recognition by ZER1/ZYG11B in cells. We found that ZER1/ZYG11B is able to target the non-acetylation of small Nt-residue degrons for degradation in NatA-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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:38:33.016.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	wenyi mi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-12 08:29:50	ID requested
1	2023-03-10 23:33:29	announced
⏵ 2	2023-11-14 08:38:33	announced	2023-11-14: Updated project metadata.

Li Y, Zhao Y, Yan X, Ye C, Weirich S, Zhang B, Wang X, Song L, Jiang C, Jeltsch A, Dong C, Mi W, recognizes small N-terminal residues for degradation. Nat Commun, 13(1):7636(2022) [pubmed]

submitter keyword: N-terminal acetylation,Nt-Ser,CRL2ZER1/ZYG11B

Wenyi Mi
contact affiliation	The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University General Hospital, Department of Immunology, Tianjin Medical University, Tianjin, 300070, China
contact email	wenyi.mi@tmu.edu.cn
lab head
wenyi mi
contact affiliation	Tianjin Medical University
contact email	wenyi.mi@tmu.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD037312

PRIDE project URI

• PRIDE
  1. PXD037312
     1. Label: PRIDE project
     2. Name: CRL2ZER1/ZYG11B recognizes small N-terminal residues for degradation