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Structural Changes in Cadherin Influence Loss of Adhesion Phenotype

Discover the correlation between loss of adhesion phenotype and conservation of extracellular region & C-terminus in cadherin proteins. Explore implications for cancer, healthy human physiology, and disease-related protein sets. Conduct sequence alignments and analyze structural differences to understand roles in cell adhesion and mobility. Valuable data sets and tools provided for comprehensive research. Acknowledgments to BioQUEST Instructors and ASM Facilitators.

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Structural Changes in Cadherin Influence Loss of Adhesion Phenotype

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  1. Loss of Adhesion Phenotype Correlated with Loss of Conservation of Extracellular Region and C-terminus in Cadherin [Picture from wikipedia] Alyssa Bumbaugh Scott H. Harrison Pennsylvania State University, Altoona College Indiana University Purdue University Indianapolis Asit Saha Central State University, Wilberforce Ohio ASM/BioQUEST March 7, 2008 Bioinformatics Institute Group Research Project Harrison Bumbaugh B Q * Saha *LABORATORIES“Rideo, Ergo sum” est. 2008

  2. Our Study • - Profiling theTwo Roles for Cadherin in Healthy Human Physiology-RSCB Protein Data Bank (http://www.rscb.org) - showed structural differences between regular E-cadherin and N-cadherin related to respective roles of the cadherin protein for: a) cell-to-cell adhesion; and b) mobility. • - Finding Healthy and Disease-Related Protein Sets -Use PIR (Protein Information Resource; http://pir.georgetown.edu) and HIP2 (Healthy Human Individuals’ Integrated Plasma Protein; http://bio.informatics.iupui.edu/HIP2) to find two related sets of cadherin proteins (a putative disease set and a putative healthy set) based on MS/MS detection counts of peptides. • - Inspecting Sequence Alignments for Correlation with Structural and Indications of Different Roles -Alignment with CLUSTALW (using http://biologyworkbench.sdsc.edu); Local regional alignments with SIM - Local similarity program; http://www.expasy.ch/tools/sim-prot.html.

  3. Cadherin, a dual role for adhesion and mobility/lubrication membrane • = loss of structure of extracellular domainand loss of C-terminus adhesion sequence • Cancer implicated with N-cadherin being expressed in breast tissue [Nieman et al, 1999; Hazan et al, 2000] • One allele deleted and the other mutated of cadherin also corresponds with cancer [Berx and Van Roy, 2001] Extracellular regions intracellular intracellular Neural cadherin [Made with http://consurf.tau.ac.il] Epithelial cadherin

  4. Sequence Alignment of Cadherin Proteins - Putative Disease Set of Cadherin Proteins based on Reduced MS/MS Detection Counts in Healthy Human Individual's Integrated Plasma Proteome Database (http://bio.informatics.iupui.edu/HIP2/)

  5. Neighbor-joining Tree of “Healthy” versus “Disease” Sets of Cadherin Proteins 38 39 26 0 15 0 0 2 2 • Neighbor-joining tree based on 500 bootstrap replications • Cadherin from disease cohort indicated with solid circle • Cadherin from healthy cohort indicated with open circle • Detection counts in Healthy Human Individual's Integrated Plasma Proteome Database (http://bio.informatics.iupui.edu/HIP2/) shown in blue

  6. 20 consecutive locally aligned regions for pairwise protein comparisons(40 to 180 aa windows)…Within-Group Comparisons vs vs

  7. 20 consecutive locally aligned regions for pairwise protein comparisons (40 to 180 aa windows)…a Between-Group Comparison

  8. Conclusions • Loss of conservation trends to the latter portion (toward the C-terminus) of the cadherin protein when there is association with motility and disease. • This may enable prognosis of cellular phenotype of cancer cells and their invasive motility.

  9. Acknowledgements Our BioQUEST Instructors and ASM Facilitators! • Sam Donovan • Michelle Godinez • Brad Goodner • Kelly Gull • John Jungck • Anton Weisstein

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