What Is the Structure of SAMHD1 and When is it Expressed?


SAMHD1, or Sterile Alpha Motif and Histidine/Aspartate domain-containing protein 1, is a dimeric enzyme with phosphohydrolase and nuclease activity that functions as a blockade for virus replication in dendritic cells, monocytes, and macrophages. Its activity is regulated through phosphorylation of Threonine 529, occurring only in cycling cells. Therefore, despite ubiquitous SAMHD1 expression in cycling and non-cycling cells, only the latter express enzymatically active protein.

How Does SAMHD1 function?


Nuclease and phosphohydrolase activity are both exhibited by SAMHD1. The phosphohyrolase activity of SAMHD1 resides in the Histadine-aspartate (HD) domain, which dismantles nucleotide triphosphates that are necessary for reverse transcriptase virus replication into unusable triphosphate and nucleoside groups. As a result, the levels of nucleotide triphosphates are sub-optimal for the synthesis of viral DNA, preventing replication.

This phosphohydrolase activity regulates replication of viruses like HIV, murine leukemia virus, and herpes simplex virus type 1. 

What Other Roles Does SAMHD1 Have In the Body?

Mutations of SAMHD1 have been implicated in Aicardi-Goutieres syndrome (AGS) - an autoimmune disorder in which interferon production is deregulated. Though the pathological role that SAMHD1 plays in the disease is unclear, the protein’s importance in immune system function is indisputable.

Why is SAMHD1 an Important Biomarker for HIV Research? 

Antibodies can be used to determine the presence of the phosphorylated, and therefore active, form of SAMHD1, By measuring its presence, it is possible to extrapolate information about HIV proliferation and it's state in different types of tissues and cells.

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