1S9Z

SYNTHETIC 17 AMINO ACID LONG PEPTIDE THAT FORMS A NATIVE-LIKE COILED-COIL AT AMBIENT TEMPERATURE AND AGGREGATES INTO AMYLOID-LIKE FIBRILS AT HIGHER TEMPERATURES.

Summary for 1S9Z

• Entry DOI: 10.2210/pdb1s9z/pdb
• Descriptor: SYNTHETIC COILED-COIL PEPTIDE, SODIUM ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: de novo protein
• Total number of polymer chains: 1
• Total formula weight: 2171.84

Authors

Kammerer, R.A.,Kostrewa, D.,Zurdo, J.,Detken, A.,Garcia-Echeverria, C.,Green, J.D.,Muller, S.A.,Meier, B.H.,Winkler, F.K.,Dobson, C.M.,Steinmetz, M.O. (deposition date: 2004-02-06, release date: 2004-04-06, Last modification date: 2024-10-30)

Primary citation

Kammerer, R.A.,Kostrewa, D.,Zurdo, J.,Detken, A.,Green, J.D.,Meier, B.H.,Winkler, F.K.,Dobson, C.M.,Steinmetz, M.O.
Exploring amyloid formation by a de novo design
Proc.Natl.Acad.Sci.USA, 101:4435-4440, 2004

PubMed Abstract: Protein deposition as amyloid fibrils underlies many debilitating human disorders. The complexity and size of disease-related polypeptides, however, often hinders a detailed rational approach to study effects that contribute to the process of amyloid formation. We report here a simplified peptide sequence successfully designed de novo to fold into a coiled-coil conformation under ambient conditions but to transform into amyloid fibrils at elevated temperatures. We have determined the crystal structure of the coiled-coil form and propose a detailed molecular model for the peptide in its fibrillar state. The relative stabilities of the two structural forms and the kinetics of their interconversion were found to be highly sensitive to small sequence changes. The results reveal the importance of specific packing interactions on the kinetics of amyloid formation and show the potential of this exceptionally favorable system for probing details of the molecular origins of amyloid disease.

PubMed: 15070736
DOI: 10.1073/pnas.0306786101

Experimental method

X-RAY DIFFRACTION (2.01 Å)