Cell Biology Commons^™

Identification Of An Archaeal Presenilin-Like Intramembrane Protease, Celia Torres-Arancivia, Carolyn M. Ross, Jose Chavez, Zahra Assur, Georgia Dolios, Filippo Mancia, Iban Ubarretxena-Belandia

Publications and Research

Background: The GXGD-type diaspartyl intramembrane protease, presenilin, constitutes the catalytic core of the c-secretase multi-protein complex responsible for activating critical signaling cascades during development and for the production of b-amyloid peptides (Ab) implicated in Alzheimer’s disease. The only other known GXGD-type diaspartyl intramembrane proteases are the eukaryotic signal peptide peptidases (SPPs). The presence of presenilin-like enzymes outside eukaryots has not been demonstrated. Here we report the existence of presenilin-like GXGD-type diaspartyl intramembrane proteases in archaea.

Methodology and Principal Findings: We have employed in vitro activity assays to show that MCMJR1, a polytopic membrane protein from the archaeon Methanoculleus marisnigri JR1, …

Yeast Cell Adhesion Molecules Have Functional Amyloid-Forming Sequences, Caleen B. Ramsook, Cho Tan, Melissa C. Garcia, Raymond Fung, Gregory Soybelman, Ryan Henry, Anna Litewka, Shanique O’Meally, Henry N. Otoo, Roy A. Khalaf, Anne M. Dranginis, Nand K. Gaur, Stephen A. Klotz, Jason M. Rauceo, Chong K. Jue, Peter N. Lipke

Publications and Research

The occurrence of highly conserved amyloid-forming sequences in Candida albicans Als proteins (H. N. Otoo et al., Eukaryot. Cell 7:776–782, 2008) led us to search for similar sequences in other adhesins from C. albicans and Saccharomyces cerevisiae. The beta-aggregation predictor TANGO found highly beta-aggregation-prone sequences in almost all yeast adhesins. These sequences had an unusual amino acid composition: 77% of their residues were beta-aggregation aliphatic amino acids Ile, Thr, and Val, which is more than 4-fold greater than their prevalence in the S. cerevisiae proteome. High beta-aggregation potential peptides from S. cerevisiae Flo1p and C. albicans Eap1p rapidly formed insoluble …

Structure And Function Of Glycosylated Tandem Repeats From Candida Albicans Als Adhesins, Aaron T. Frank, Caleen B. Ramsook, Henry N. Otoo, Cho Tan, Gregory Soybelman, Jason M. Rauceo, Nand K. Gaur, Stephen A. Klotz, Peter N. Lipke

Publications and Research

Tandem repeat (TR) regions are common in yeast adhesins, but their structures are unknown, and their activities are poorly understood. TR regions in Candida albicans Als proteins are conserved glycosylated 36-residue sequences with cell-cell aggregation activity (J. M. Rauceo, R. De Armond, H. Otoo, P. C. Kahn, S. A. Klotz, N. K. Gaur, and P. N. Lipke, Eukaryot. Cell 5:1664–1673, 2006). Ab initio modeling with either Rosetta or LINUS generated consistent structures of three-stranded antiparallel beta-sheet domains, whereas randomly shuffled sequences with the same composition generated various structures with consistently higher energies. O- and N-glycosylation patterns showed that each TR …