Genome complexity: how to repair DNA (Introduction)

by David Turell , Thursday, September 03, 2015, 18:01 (3370 days ago) @ David Turell

Another study looks at the complex arrangements of enzymes that helps manage DNA repair:-http://phys.org/news/2015-09-decodes-protein-complex-dna.html-"One enzyme in particular, BRCC36, removes a specific type of ubiquitin that is central to DNA damage repair as well as inflammatory responses. But BRCC36 doesn't act on its own—it functions as part of a complex comprised of several other proteins, one of which is KIAA0157. But how these two work together has remained unclear. Now, thanks to work performed in collaboration between researchers at the Perelman School of Medicine at the University of Pennsylvania and the Lunenfeld-Tanenbaum Research Institute in Toronto, the mechanism is coming into focus.-***-"They found that BRCC36 and KIAA0157 are structurally related proteins, but while the BRCC36 is capable of removing ubiquitin (generally called a DUB for its deubiquitinating function), KIAA0157, is not quite up for that job since it does not bind the metal ions necessary for removing ubiquitin, so is referred to as a "pseudo-DUB."-"By comparing high-resolution structures of two complexes - one containing both a DUB and a pseudo-DUB, and two copies of an inactive DUB by itself—the team determined that KIAA0157 alters the shape of the BRCC36 active site, by swinging an amino acid into position to make the complex able to catalyze chemical reactions.-"They also found that the complete, functional complex contains two BRCC36-KIAA0157 molecule pairs, a symmetrical configuration the authors call a "super-dimer."-***-"According to Greenberg, BRCC36-KIAA0157 is just one of many deubiquitinating enzyme complexes present in cells of complex organisms: "It turns out to be a general mechanism of how this class of deubiquitinating enzymes works." Given the similarity of these related proteins to one another, knowing the structure and mechanism of BRCC36-KIAA0157 should enable researchers to better model the structures of related complexes, and also probe their mechanisms."