Dataset Information

Guanine-containing ssDNA and RNA induce dimeric and tetrameric SAMHD1 in cryo-EM and binding studies

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Escherichia Coli

SUBMITTER: Benjamin Orris

LAB HEAD: James T. Stivers

PROVIDER: PXD043587 | Pride | 2023-11-13

REPOSITORIES: pride

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			Action	DRS
	SAMHD1_PostNi_112922_01.msf	Msf
	SAMHD1_PostNi_112922_01.raw	Raw
	SAMHD1_PostNi_112922_02.raw	Raw
	SAMHD1_PostNi_112922_03.raw	Raw
	SAMHD1_PostSEC_112922_01.msf	Msf

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Publications

Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.

Orris Benjamin B Sung Min Woo MW Bhat Shridhar S Xu Yingrong Y Huynh Kevin W KW Han Seungil S Johnson Darren C DC Bosbach Benedikt B Shields David J DJ Stivers James T JT

Nucleic acids research 20231201 22

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 in cryo-EM and biochemical studies that the guanine-specific A1 activator site of each SAMHD1 monomer ...[more]

PMID: 37930833

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