The bioinformatics and evolution of fungal cell wall proteins.
Item
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Title
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The bioinformatics and evolution of fungal cell wall proteins.
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Identifier
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AAI3325433
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identifier
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3325433
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Creator
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Coronado, Juan E.
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Contributor
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Adviser: Peter N. Lipke
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Bioinformatics | Biology, Molecular | Biology, Cell
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Abstract
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Cell walls are hallmarks of the kingdom Fungi. Cell walls provide a myriad of functions for fungi: from osmotic protection to signal transduction. The mediators of these functions are cell wall proteins (CWPs) that are embedded in the carbohydrate network of the cell wall. Cell wall proteins have distinct characteristics: a secretory signal sequence in the N-terminus, repetitive and/or simple sequences, N and O glycosylation sites, disulfide-forming cysteine residues, and may have a membrane-anchoring glycosyl phosphatidyl inositol addition signal (GPI) at the C-terminus of the proteins.;Because CWPs often contain simple or low-complexity sequences rich in a few amino acids, sequence comparison tools- such as FASTA and BLAST- tend to align the most common residues in nonhomologous positions. These random alignments generate high similarity scores that deviate from the expected extreme value distribution and produce false statistical significance values (e values). We tested scoring matrices that compensate for the overrepresentation of some amino acids in any query sequence based on expected score (E) and information entropy (Q). These matrices were tested for sensitivity in finding true homologs, discrimination against nonhomologous and random sequences, conformance to the extreme value distribution, and accuracy of E values. Of the tested matrices, two matrices (called E and gtQ) gave reliable alignments in BLAST and FASTA searches, identified a consistent set of paralogs of the yeast cell wall test set proteins, and improved the consistency of secondary structure predictions for cell wall proteins.;Iterative searches of the S. cerevisiae proteome with the modified matrices yielded a total of 171 known and putative cell wall proteins. The aligned segments were repeatedly subdivided and catalogued to identify 217 recurrent sequence motifs of length 8 amino acids or greater. Ninety-five percent (95%) of these motifs occur in more than one cell wall protein. The prevalence of these motifs supports the idea of fungal cell wall proteins as assemblies of recurrent building blocks, which through evolution can combinatorially produce many variants that can undergo natural selection.;When S. cerevisiae CWPs were compared with 17 other fungal proteomes, we found that cell wall protein profiles were consistent with fungal phylogenetic profiles, and only carbohydrate-modifying enzymes or chaperones were present in all or a majority of the fungal species. The 171 CWPs and 16 biosynthesis and biogenesis proteins were compared to the non-redundant (NR) database to look at the presence or absence of the proteins in other kingdoms of life. We found that carbohydrate-processing proteins and chaperones were the most conserved in other kingdoms, while invasins and adhesins were conserved only in less evolutionarily distant genera. The distribution of the cell wall related proteins provides evidence for a cell walled ancestor to all cells.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
