NR AIMG
AU Mo,H.; Moore,R.C.; Cohen,F.E.; Westaway,D.; Prusiner,S.B.; Wright,P.E.; Dyson,H.J.
TI Two different neurodegenerative diseases caused by proteins with similar structures
QU Proceedings of the National Academy of Sciences of the United States of America 2001 Feb 27; 98(5): 2352-7
PT journal article
AB The downstream prion-like protein (doppel, or Dpl) is a paralog of the cellular prion protein, PrPc. The two proteins have approximately 25% sequence identity, but seem to have distinct physiologic roles. Unlike PrPc, Dpl does not support prion replication; instead, overexpression of Dpl in the brain seems to cause a completely different neurodegenerative disease. We report the solution structure of a fragment of recombinant mouse Dpl (residues 26-157) containing a globular domain with three helices and a small amount of beta-structure. Overall, the topology of Dpl is very similar to that of PrPc. Significant differences include a marked kink in one of the helices in Dpl, and a different orientation of the two short beta-strands. Although the two proteins most likely arose through duplication of a single ancestral gene, the relationship is now so distant that only the structures retain similarity; the functions have diversified along with the sequence.
MH Amino Acid Sequence; Animal; Base Sequence; Cloning, Molecular; DNA Primers; Disulfides/chemistry; Human; Models, Molecular; Molecular Sequence Data; Neurodegenerative Diseases/*etiology/metabolism; Nuclear Magnetic Resonance, Biomolecular; PrPc Proteins/chemistry/*physiology; Prions/chemistry/genetics/*physiology; Protein Conformation; Recombinant Proteins/chemistry/genetics/metabolism; Sequence Homology, Amino Acid; Support, U.S. Gov't, P.H.S.
AD Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
SP englisch
PO USA