4PER

Structure of Gallus gallus ribonuclease inhibitor complexed with Gallus gallus ribonuclease I

Summary for 4PER

• Entry DOI: 10.2210/pdb4per/pdb
• Related: 4PEQ
• Descriptor: Ribonuclease Inhibitor, Angiogenin (3 entities in total)
• Functional Keywords: leucine-rich repeat, protein-protein complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Gallus gallus (Chicken); More
• Cellular location: Cytoplasmic vesicle, secretory vesicle lumen : P27043
• Total number of polymer chains: 2
• Total formula weight: 63287.66

Authors

Bianchetti, C.M.,Lomax, J.E.,Raines, R.T.,Fox, B.G. (deposition date: 2014-04-24, release date: 2014-06-25, Last modification date: 2024-10-23)

Primary citation

Lomax, J.E.,Bianchetti, C.M.,Chang, A.,Phillips, G.N.,Fox, B.G.,Raines, R.T.
Functional evolution of ribonuclease inhibitor: insights from birds and reptiles.
J.Mol.Biol., 426:3041-3056, 2014

PubMed Abstract: Ribonuclease inhibitor (RI) is a conserved protein of the mammalian cytosol. RI binds with high affinity to diverse secretory ribonucleases (RNases) and inhibits their enzymatic activity. Although secretory RNases are found in all vertebrates, the existence of a non-mammalian RI has been uncertain. Here, we report on the identification and characterization of RI homologs from chicken and anole lizard. These proteins bind to RNases from multiple species but exhibit much greater affinity for their cognate RNases than for mammalian RNases. To reveal the basis for this differential affinity, we determined the crystal structure of mouse, bovine, and chicken RI·RNase complexes to a resolution of 2.20, 2.21, and 1.92Å, respectively. A combination of structural, computational, and bioinformatic analyses enabled the identification of two residues that appear to contribute to the differential affinity for RNases. We also found marked differences in oxidative instability between mammalian and non-mammalian RIs, indicating evolution toward greater oxygen sensitivity in RIs from mammalian species. Taken together, our results illuminate the structural and functional evolution of RI, along with its dynamic role in vertebrate biology.

PubMed: 24941155
DOI: 10.1016/j.jmb.2014.06.007

Experimental method

X-RAY DIFFRACTION (1.92 Å)