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What Can We Learn From Highly Connected ß-Rich Structures for Structural Interface Design?

  • Ugur Emekli
  • K. Gunasekaran
  • Ruth Nussinov
  • Turkan Haliloglu
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 474)

Summary

Most hubs' binding sites are able to transiently interact with numerous proteins. We focus on β-rich hubs with the goal of inferring features toward design. Since they are able to interact with many partners and association of β-conformations may lead to amyloid fibrils, we ask whether there is some property that distinguishes them from low-connectivity β-rich proteins, which may be more interaction specific. Identification of such features should be useful as they can be incorporated in interface design while avoiding polymerization into fibrils. We classify the proteins in the yeast interaction map according to the types of their secondary structures. The small number of the obtained β-rich protein structures in the Protein Data Bank likely reflects their low occurrence in the proteome. Analysis of the obtained structures indicates that highly connected β-rich proteins tend to have clusters of conserved residues in their cores, unlike β-rich structures with low connectivity, suggesting that the highly packed conserved cores are important to the stability of proteins, which have residue composition and sequence prone to β-structure and amyloid formation. The enhanced stability may hinder partial unfolding, which, depending on the conditions, is more likely to lead to polymerization of these sequences.

Key Words

β-Structures connectivity hubs interface design network yeast network 

Notes

Acknowledgments

The dataset of proteins used in this study was generated by Kristina Rogale. We thank Isil Ulug in the analysis for bulges. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. T. Haliloglu acknowledges the Turkish Academy of Sciences in the framework of the Young Scientist Award Program (EA-TUBA-GEBIP/2001-1-1), State Planning Organization grants 03K120250 and EU_FP6-2004-ACC-SSA-2: Project 517991.

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Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Ugur Emekli
    • 1
  • K. Gunasekaran
    • 2
  • Ruth Nussinov
    • 3
  • Turkan Haliloglu
    • 1
  1. 1.Polymer Research Center and Chemical Engineering DepartmentBogaziçi UniversityIstanbulTurkey
  2. 2.Basic Research ProgramSAIC-Frederick Inc., Center for Cancer Research Nanobiology Program, NCI-FrederickFrederick
  3. 3.Center for Cancer Research Nanobiology Program, SAIC-Frederick, National Cancer Institute. Department of Human GeneticsMedical School, Tel Aviv UniversityTel AvivIsrael

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