6BRH

The SAM domain of mouse SAMHD1 is critical for its activation and regulation

Summary for 6BRH

• Entry DOI: 10.2210/pdb6brh/pdb
• Related: 6BRG
• Descriptor: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, MAGNESIUM ION, 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: dntpase, allosteric regulation, binding sites, mouse, models, molecular, protein conformation, protein multimerization, hydrolase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 156156.53

Authors

Buzovetsky, O.,Tang, C.,Knecht, K.M.,Antonucci, J.M.,Wu, L.,Ji, X.,Xiong, Y. (deposition date: 2017-11-30, release date: 2018-02-14, Last modification date: 2023-10-04)

Primary citation

Buzovetsky, O.,Tang, C.,Knecht, K.M.,Antonucci, J.M.,Wu, L.,Ji, X.,Xiong, Y.
The SAM domain of mouse SAMHD1 is critical for its activation and regulation.
Nat Commun, 9:411-411, 2018

PubMed Abstract: Human SAMHD1 (hSAMHD1) is a retroviral restriction factor that blocks HIV-1 infection by depleting the cellular nucleotides required for viral reverse transcription. SAMHD1 is allosterically activated by nucleotides that induce assembly of the active tetramer. Although the catalytic core of hSAMHD1 has been studied extensively, previous structures have not captured the regulatory SAM domain. Here we report the crystal structure of full-length SAMHD1 by capturing mouse SAMHD1 (mSAMHD1) structures in three different nucleotide bound states. Although mSAMHD1 and hSAMHD1 are highly similar in sequence and function, we find that mSAMHD1 possesses a more complex nucleotide-induced activation process, highlighting the regulatory role of the SAM domain. Our results provide insights into the regulation of SAMHD1 activity, thereby facilitating the improvement of HIV mouse models and the development of new therapies for certain cancers and autoimmune diseases.

PubMed: 29379009
DOI: 10.1038/s41467-017-02783-8

Experimental method

X-RAY DIFFRACTION (3.4 Å)