User:Birger Lenz/Sandbox 4x09

4x09 is the human RNase 6.

Function

Human RNase 6 is a cationic secreted protein that belongs to the RNase A superfamily (DNase and protease-free, RNase 6 is an endoribonuclease that specifically degrades single-stranded RNA at C and U residues). Many members of this family have a role in innate immunity and present some conservations like the disulfide bonding pattern and the catalytic triad. The protein is secreted in neutrophils and monocytes (immunity cells) and so has a role in host defense (present after the bacterial infection and specially with uropathogenic bacteria). The RNase has been revealed to be efficient against Gram-negative and Gram-positive species and its mechanism of action was characterized using a membrane model.

Structural Highlights

The complete RNase is 1.72 Å tall and is composed of 128 amino acids (17kDa). It is organized in and . The structure forms an overall kidney-shaped globe which characterizes the RNases A. 4 disulfide bonds are responsible for this structure. There is another possible conformation for the N-terminal domain in which the Trp folds back towards the protein core. The crystal structure shows a secondary active site which allows to catalyze the hydrolysis of the target RNA. The protein was crystallized in presence of ammonium sulfate and were identified (interactions with residues His37, His40, Arg67 and His68 which are cationic residues, exposed at the protein surface, and interactions with the residues His16, His123 and Gln15 in the main active site, conserved in all RNase A).

Disease

RNase 6 is related to the defense of the organism against some pathogens. Its transcription happens in different tissues, but its expression is mainly in the neutrophils, granulocytes & monocytes. It has been put in evidence, in vitro, that the enzyme has an antimicrobial activity against several uropathogenic bacteria. Indeed, RNase 6, which can be secreted by the macrophages, is a protein which influences the gram-negative membranes. Its effect is to agglutinate the pathogen bacteria and to permeabilize their membranes. Furthermore, it has been put in evidence in vitro that the infection of HIV on its target cells is inhibited in presence of RNase 6.