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Discovering Protein Interactions and Characterizing Protein Function Using HaloTag Technology
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Unique function words characterize genomic proteins.

Andrea Scaiewicz1, Michael Levitt1

  • 1Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 michael.levitt@stanford.edu scaiewicz@stanford.edu.

Proceedings of the National Academy of Sciences of the United States of America
|June 14, 2018
PubMed
Summary
This summary is machine-generated.

Protein sequence analysis reveals that a limited set of unique function words (UFWs) combine to create diverse multiple domain architectures (MDAs), driving genomic diversity. This combinatorial approach explains the vast array of protein functions observed.

Keywords:
domain architecturefunctional profilesgenomic sequencesprotein universeshared function

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • The number of protein sequences has rapidly increased, with most containing conserved motifs.
  • Conserved domain architecture retrieval tool (CDART) identifies sequence motifs, but profile redundancy complicates functional analysis.

Purpose of the Study:

  • To develop a method to reduce redundancy in protein sequence motif profiles.
  • To analyze the impact of this reduction on understanding protein functional complexity and genomic diversity.

Main Methods:

  • Full-linkage clustering of redundant CDART profiles using maximum disjoint cliques.
  • Identification of unique function words (UFWs) as representative profiles.
  • Analysis of UFWs and multiple domain architectures (MDAs) in protein sequences from 2009-2016.

Main Results:

  • The number of UFWs increased by 30%, slower than the 80% increase in CDART profiles, suggesting saturation.
  • Multiple domain architectures (MDAs) formed by combinatorial arrangements of UFWs increased proportionally to total sequences.
  • Eukaryotes and prokaryotes share similar UFWs but exhibit distinct MDAs, indicating divergent functional strategies.

Conclusions:

  • A limited set of UFWs, when combinatorially arranged into MDAs, accounts for the vast genomic diversity of protein sequences.
  • The distinct combinatorial usage of UFWs in MDAs between eukaryotes and prokaryotes highlights species-specific functional adaptations.