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Related Experiment Videos

Structural characterization of the human proteome.

Arne Müller1, Robert M MacCallum, Michael J E Sternberg

  • 1Biomolecular Modelling Laboratory, Cancer Research UK, London, United Kingdom.

Genome Research
|November 8, 2002
PubMed
Summary

This study analyzes protein structures across species, revealing that 39% of the human proteome has known structures and 98% evolved via domain duplication. Key structural superfamilies are identified, with implications for human disease genes.

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Area of Science:

  • Comparative genomics
  • Structural biology
  • Bioinformatics

Background:

  • Understanding protein structure and function is crucial for deciphering biological processes.
  • Existing knowledge of proteomes is fragmented, with varying levels of structural and functional annotation across species.

Purpose of the Study:

  • To analyze and compare the proteomes of human, fly, worm, yeast, bacteria, and archaea.
  • To identify common structural superfamilies and their evolutionary patterns.
  • To investigate the relationship between protein structures and human disease genes.

Main Methods:

  • Analysis of three-dimensional structures of globular protein domains.
  • Sequence-based studies of proteomes.
  • Identification and frequency analysis of structural superfamilies.

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  • Comparison of domain duplication patterns across species.

    • Main Results:

    • 39% of the human proteome is assigned to known structures; 77% has functional annotation, but only 26% has identifiable sequence motifs.
    • Transmembrane proteins constitute 13% of human protein sequences, with distinct domain compositions across analyzed proteomes.
    • 98% of the human proteome likely evolved by domain duplication, with some superfamilies specific to multicellular organisms; domain repeats are more common in metazoa.

    Conclusions:

    • Significant portions of proteomes remain structurally uncharacterized or lack detailed functional motifs.
    • Domain duplication is a major evolutionary mechanism, particularly in multicellular organisms.
    • Specific structural superfamilies are associated with human disease, offering potential targets for research.