MBE Advance Access published online on November 20, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl177
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA
* To whom correspondence should be addressed. Disulfide bonds play important roles in the folding and stability of proteins and are evolutionary conserved. A classic example is RNase A (also known as bovine pancreatic ribonuclease), which contains four conserved disulfide bonds among eight 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 to RNase 8 of various monkeys and to 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 million years ago. 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 one loss and one gain of cysteine, instead of two losses or two 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.
Accepted November 15, 2006
Research Article
Disulfide-Bond Reshuffling in the Evolution of an Ape Placental Ribonuclease
Jianzhi Zhang 1 *
Jianzhi Zhang, E-mail: jianzhi{at}umich.edu
![]()
Abstract ![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
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] |
||||
