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The ribonuclease inhibitor-angiogenin complex is a protein most concentrated in human placental cells. The ribonuclease inhibitor protein and angiogenin protein have a strong affinity for each other. The main gene that codes for the ribonuclease inhibitor is RNH1. Ribonuclease also inhibits other proteins such as RNASE1 and RNASE2, so it is also important in processing RNA. Angiogenin has a sequence length of 123 and its gene name is ANG or RNASE5.

Function

The complex is responsible for protein binding and positive regulation of phosphorylation. The ribonuclease inhibitor protein binds to the angiogenin complex, a blood-vessel inducing protein, to inhibit it. Angiogenin is able to promote growth of blood vessels by promoting rRNA transcription. Under normal growth conditions, ANG is located in the nucleus away from the ribonuclease inhibitor to allow for prolific rRNA transcription. However, during periods of stress nuclear ANG is associated with ribonuclease inhibitor in the cytoplasm. This allows ribonuclease inhibitor to inhibit ANG, and prevent excess rRNA transcription allowing for energy to be conserved. Angiogenin also mediates the production of tiRNA, which have been shown to suppress global protein translation of both capped and uncapped mRNA. In response to stress, tiRNAs reprogram protein translation, thereby promoting cell survival. Therefore, ANG is conserved in granules in the cytoplasm to allow it to mediate tiRNA production and help the cell survive. The ribonuclease inhibitor is key in preventing overproduction of the ANG during stress conditions.

Relevance

Angiogenin has been known to be involved in normal and tumor growth during angiogenesis. The presence of inhibitors, such as ribonuclease inhibitor, blocks angiogenin and limits blood vessel growth. This can therefore curb proliferation of cancer cells. Malfunctions in angiogenin are also a main cause of amyotrophic lateral sclerosis (ALS), and is the main 'loss-of-function' mutation associated with the disorder. ANG also is a contributor to other neurodegenerative diseases.

Structural highlights

The complex consists of two distinct protein molecules: ribonuclease inhibitor and angiogenin. The ribonuclease inhibitor has two chains, . The angiogenin molecule consists of two chains, . Chains C and F correspond to the water molecules associated with the complex. The ribonuclease inhibitor molecule is particularly rich in repeats. Because the complex consists of the two molecules, there are sites of high interaction. The places of strongest contact are between the residue in angiogenin and in ribonuclease inhibitor.