Protein Modification part 2 of 3

Histone methylation -making binding relationships
by: Andrew J Bannister

The nucleosome is the fundamental unit of chromatin and its high‑resolution X‑ray crystal structure was solved in 19971. This remarkable achievement showed the elegant and highly ordered packing of histones within 1.75 turns of DNA and it hinted at ways in which histones may be involved in regulating higher‑order chromatin structure. Perhaps most striking is the way in which histone N‑terminal tails protrude from their own nucleosome and, in some cases, make contact with adjacent nucleosomes. Simple extrapolation from this observation has implicated these interactions in higher‑order chromatin regulation and many considered it likely that PTM (post‑translational modification) of the tails would affect inter‑nucleosomal stability and hence DNA processes such as transcription. Histone tails actually support multiple PTMs, including acetylation, phosphorylation and methylation. This brief overview considers histone methylation and discusses what we understand concerning its role.

Protein phosphorylation -
by: Dario R. Alessi and Elton Zeqiraj

At first glance, the odds that the introduction of a diminutive and unsuspicious phosphoryl group on to a hydroxy‑containing side chain of a much larger protein molecule would be selected by Nature as the most widely deployed mechanism to control biological processes, and be responsible for many major diseases, seems unlikely. However, this process termed protein phosphorylation is a vital regulator of almost all events that take place in eukaryotic organisms. This review outlines what phosphorylation is, how it is regulated and why disruptions of the network of enzymes and proteins that regulate the phosphorylation are a principal cause of many maladies. It also discusses how advances are leading to exciting strategies to develop drugs to treat diseases caused by disruptions of protein phosphorylation.