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MBE Advance Access originally published online on November 20, 2006
Molecular Biology and Evolution 2007 24(2):505-512; doi:10.1093/molbev/msl177
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

Disulfide-Bond Reshuffling in the Evolution of an Ape Placental Ribonuclease

Jianzhi Zhang

Department of Ecology and Evolutionary Biology, University of Michigan

E-mail: jianzhi{at}umich.edu.

Accepted for publication November 15, 2006.

Disulfide bonds play important roles in the folding and stability of proteins and are evolutionarily conserved. A classic example is RNase A (also known as bovine pancreatic ribonuclease), which contains 4 conserved disulfide bonds among 8 cysteines. However, human RNase 8, a paralog of RNase A uniquely expressed in the placenta, has lost one of the conserved cysteines but gained another, when compared with RNase 8 of various monkeys and with RNase A. We here show that both the loss and gain of the cysteines in human RNase 8 occurred in the common ancestor of African great apes (humans, chimps, and gorillas) 7–13 MYA. Computational predictions suggest changes of disulfide bonding by these cysteine substitutions. Site-directed mutagenesis indicates that if the ribonucleolytic activity is essential for RNase 8's function, the gain of the cysteine must have preceded the loss. Human RNase 8 represents one of the first examples in which the presumable evolutionary change of a disulfide bond involves 1 loss and 1 gain of cysteine, instead of 2 losses or 2 gains. Our results provide the foundation for detailed analysis toward understanding the impact of disulfide-bond reshuffling on the structure, function, and evolution of proteins in general and human RNase 8 in particular.

Key Words: ribonuclease • primate • disulfide bond

Andriana Briscoe, Associate Editor


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S. Cho and J. Zhang
Zebrafish Ribonucleases Are Bactericidal: Implications for the Origin of the Vertebrate RNase A Superfamily
Mol. Biol. Evol., May 1, 2007; 24(5): 1259 - 1268.
[Abstract] [Full Text] [PDF]



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