Ribonuclease Inhibitor-Angiogenin Complex is a complex of Human placental RNase inhibitor (hRI) and the blood vessel-inducing protein human Angiogenin. RNase inhibitor neutralizes the angiogenic, ribonucleolytic, and phospholipase C-stimulating activities of Angiogenin. These proteins are easily complexed as they have one of the strongest protein-protein affinities for each other of any protein complex.
Function
Protein binding: Selectively binds to other protein complexes non-covalently. Angiogenin promotes angiogenesis which is a stimulator of new blood vessels along with rRNA. RNH1 works to inhibit an endonuclease that cleaves phosphodiester bonds, RNASE1, and RNASE2 . The overall function of the complex is to inhibit Angiogenin.
Disease
has a role in cancers and tumor growth. A mutation in 1a4y which results in increased activity of Ang could lead to tumor growth. Angiogenin stimulates rRNA transcription when in cancer cells as it binds to ribosomal DNA, specifically research has shown that the highest upregulated gene in Akt-driven prostate intraepithelial neoplasia (PIN) in mice is Ang. Ang has also been theorized as a protector of the central nervous system and thus under-production of 1a4y may result in limited Ang and thus neurodegenerative diseases.
Relevance
Mutations in Angiogenin can result in drastic impacts on human health. As stated above, over or under production/activity can result in a broad range of diseases from cancers to neurodegenerative disorders. Pharmaceutical products could utilize target angiogenin, especially in cases of prostate cancer which it has been found to play a major role. The neutrilization or diminishing of lone angiogenin in these cases could limit tumor growth and the effectiveness of cancer cells. In addition pharmaceuticals could spur the complexing of Angiogenin and Ribonuclease Inhibitor 1.
Structural highlights
-The unusual non-globular structure of ribonuclease inhibitor, its solvent parallel and the conformational flexibility of the structure are used in the interaction. In addition The RI has a repeating sequence of Leucine repeats which have the distinguishing factor of yielding vast surface areas and thus better fostering protein-protein interactions. These structures make the ribonuclease inhibitor an effective binding protein. The beta-strands hydrogen bond (usually 3) to form beta sheets which make up the backbone of the protein. Surrounding the backbone are alpha helices. Ribonuclease inhibitor is encoded by the gene RNH1.
Angiogenin- Encoded for by the ANG gene. It makes up the b and e chains of the 1a4y protein. Residue numbers 25 to 147 consist of the Angiogenin protein.
