Avtor/Urednik		Mihelič, Marko
Naslov		Interakcija mišjih in človeških katepsinov S in L z inhibitornim fragmentom invariantne verige p41 asociirane z molekulami MHC razreda II
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Univerza v Ljubljani, Medicinska fakulteta
Leto izdaje		2007
Obseg		str. 64
Jezik		slo
Abstrakt		Efficiency of endosomal antigen presentation depends on the activity of cysteine cathepsins, which are involved in the processes of MHC class II maturation and preparation of antigenic peptides. Previously it was shown that the p4` fragment of MHC class II associated invariant chain acts as a strong and specific inhibitor of cathepsin L, while the activity of the closely related cathepsin S remains unaffected. On the basis of the crystal structure of the complex between the inhibitory fragment of human p41 invariant chain and cathepsin L, the mechanism for this selectivity was preposed. 3D model of the putative complex between human cathepsin S and inhibitory fragment pointed out several amino acid residues on the surface of the human cathepsin S that sterically as well as eletrostatically prevent approach of the inhibitory fragment. In the last decade techniques of recombinant DNA enabled us to discover a new set of cysteine cathepsins. Determination of their specific roles in the processes of invariant chain degradation raised the question of what are the mechanisms of the regulation of their proteolytic activity within the endosomes. We have shown that, the p41 inhibitory fragment inhibits not only cathepsins L and H but also cathepsins V, F and K with interaction constants within in-vivo relevant nanomolar range. Therfore, the p41 inhibitory fragment can not be considered as a cathepsin L specific inhibitor, but is probably playing a more general regulatory role within enodsomes. (Abstract truncated at 2000 characters)
Deskriptorji		CATHEPSINS CYSTEINE PROTEINASE INHIBITORS GENES, MHC CLASS II ENDOSOMES PLASMIDS SEQUENCE ALIGNMENT POLYMERASE CHAIN REACTION BASE SEQUENCE DNA, COMPLEMENTARY TRANSFECTION