PXD032791

PXD032791 is an original dataset announced via ProteomeXchange.

Title	Structural basis of paralog-specific KDM2A/B nucleosome recognition
Description	The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. In order to define the molecular basis of acidic patch recognition proteome-wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. These KDM2 family JumonjiC (JmjC) domain lysine demethylases are critical to heterochromatin formation and are commonly misregulated in cancer. Despite fundamental roles in transcriptional regulation in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any other JmjC lysine demethylases, remain unclear. We used a covalent JmjC inhibitor to solve cryo-EM structures of KDM2A and KDM2B trapped in action on the nucleosome. Our structures show that KDM2-nucleosome binding is paralog-specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:39.092.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD032791
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dennis Goldfarb
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-24 13:36:15	ID requested
1	2023-02-14 11:03:06	announced
⏵ 2	2023-11-14 08:55:39	announced	2023-11-14: Updated project metadata.

10.6019/PXD032791;

submitter keyword: nucleosome, demethylase, KDM2B, JmjC,chromatin, acidic patch, KDM2A

Robert McGiinty
contact affiliation	1Department of Biochemistry and Biophysics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
contact email	rmcginty@email.unc.edu
lab head
Dennis Goldfarb
contact affiliation	Cell Biology and Physiology Institute for Informatics
contact email	d.goldfarb@wustl.edu
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/2023/02/PXD032791

PRIDE project URI

• PRIDE
  1. PXD032791
     1. Label: PRIDE project
     2. Name: Structural basis of paralog-specific KDM2A/B nucleosome recognition