PXD043587

PXD043587 is an original dataset announced via ProteomeXchange.

Title	Guanine-containing ssDNA and RNA induce dimeric and tetrameric SAMHD1 in cryo-EM and binding studies
Description	The dNTPase activity of tetrameric SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) plays a critical role in cellular dNTP regulation. SAMHD1 also associates with stalled DNA replication forks, DNA repair foci, ssRNA, and telomeres. The above functions require nucleic acid binding by SAMHD1, which may be modulated by its oligomeric state. Here we establish that the guanine-specific A1 activator site of each SAMHD1 monomer is used to target the enzyme to guanine nucleotides within single-stranded (ss) DNA and RNA. Remarkably, nucleic acid strands containing a single guanine base induce dimeric SAMHD1, while two or more guanines with ~20 nucleotide spacing induce a tetrameric form. A cryo-EM structure of ssRNA-bound tetrameric SAMHD1 shows how ssRNA strands bridge two SAMHD1 dimers and stabilize the structure. This ssRNA-bound tetramer is inactive with respect to dNTPase and RNase activity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:13:35.917.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Orris
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-06 12:46:14	ID requested
1	2023-11-13 15:06:06	announced
⏵ 2	2023-11-14 09:13:40	announced	2023-11-14: Updated project metadata.

Orris B, Sung MW, Bhat S, Xu Y, Huynh KW, Han S, Johnson DC, Bosbach B, Shields DJ, Stivers JT, Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1. Nucleic Acids Res, 51(22):12443-12458(2023) [pubmed]

submitter keyword: Aicardi-Goutieres Syndrome, DNA repair, RNase,SAMMHD1, HIV

James T. Stivers
contact affiliation	Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
contact email	jstivers@jhmi.edu
lab head
Benjamin Orris
contact affiliation	Johns Hopkins University
contact email	borris1@jhmi.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/2023/11/PXD043587

PRIDE project URI

• PRIDE
  1. PXD043587
     1. Label: PRIDE project
     2. Name: Guanine-containing ssDNA and RNA induce dimeric and tetrameric SAMHD1 in cryo-EM and binding studies