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Oligomerization and Auto-methylation of the Human Lysine Methyltransferase SETD6.

A new interesting article has been published in J Mol Biol. 2018 Oct 19;430(21):4359-4368. doi: 10.1016/j.jmb.2018.08.028. Epub 2018 Sep 4. and titled:

Oligomerization and Auto-methylation of the Human Lysine Methyltransferase SETD6.

Authors of this article are:

Weil LE, Shmidov Y, Kublanovsky M, Morgenstern D, Feldman M, Bitton R, Levy D.

A summary of the article is shown below:

Signaling via lysine methylation by protein lysine methyltransferases (PKMTs), has been linked to diverse biological and disease processes. The mono-methyltransferase SETD6 (SET-domain-containing protein 6) is a member of the PKMT family and was previously shown to regulate essential cellular processes such as the NF-κB, WNT and the oxidative stress pathways. However, on the biochemical level, little is known about the enzymatic mode of action of SETD6. Here we provide evidence that SETD6 forms high-molecular-weight structures. Specifically, we demonstrate that SETD6 monomeric, dimeric and trimeric forms are stabilized by the methyl donor, S-adenosyl-l-methionine. We then show that SETD6 has auto-methylation activity at K39 and K179, which serves as the major auto-methylation sites with a moderate auto-methylation activity toward K372. A point mutation at K179 but not at K39 and K372, located at the SET domain of SETD6, impaired SETD6 ability to form a trimer, strongly implying a link between the auto-methylation and the oligomerization state. Finally, by radioactive in vitro methylation experiments and biochemical kinetics analysis, we show that the auto-methylation at K39 and K179 increases the catalytic rate of SETD6. Collectively, our data support a model by which SETD6 auto-methylation and self-interaction positively regulate its enzymatic activity in vitro and may suggest that other PKMTs are regulated in the same manner.

Check out the article’s website on Pubmed for more information:

This article is a good source of information and a good way to become familiar with topics such as:

SETD6;auto-methylation;lysine methylation


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