1QJH

Protein Aggregation and Alzheimer's Disease: Crystallographic Analysis of the Phenomenon. Engineered version of the ribosomal protein S6 used as a stable scaffold to study oligomerization.

Summary for 1QJH

• Entry DOI: 10.2210/pdb1qjh/pdb
• Related: 1CQM 1CQN 1LOU 1RIS
• Descriptor: 30S ribosomal protein S6, MAGNESIUM ION (3 entities in total)
• Functional Keywords: ribosomal protein, alzheimer disease, ribosomal protein s6, oligomerization
• Biological source: Thermus thermophilus
• Total number of polymer chains: 1
• Total formula weight: 11855.01

Authors

Kristensen, O.,Otzen, D.E.,Oliveberg, M. (deposition date: 1999-06-24, release date: 2000-06-29, Last modification date: 2023-12-13)

Primary citation

Otzen, D.E.,Kristensen, O.,Oliveberg, M.
Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: a structural clue to amyloid assembly.
Proc. Natl. Acad. Sci. U.S.A., 97:9907-9912, 2000

PubMed Abstract: Limited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (beta-AP) are major obstacles to a molecular understanding of protein fibrillation and deposition processes. Here we have circumvented the solubility problem by stepwise engineering a beta-AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest beta-AP homology crystallizes as a tetramer that is linked by the beta-AP residues forming intermolecular antiparallel beta-sheets. This construct also shows increased coil aggregation during refolding, and a 14-mer peptide encompassing the engineered sequence forms fibrils. Mutational analysis shows that intermolecular association is linked to the overall hydrophobicity of the sticky sequence and implies the existence of "structural gatekeepers" in the wild-type protein, that is, charged side chains that prevent aggregation by interrupting contiguous stretches of hydrophobic residues in the primary sequence.

PubMed: 10944185
DOI: 10.1073/pnas.160086297

Experimental method

X-RAY DIFFRACTION (2.2 Å)