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Updated: May 30, 2026
14:33
Generation, Purification, and Characterization of Cell-invasive DISC1 Protein Species
Published on: August 30, 2012
Structure and evolutionary history of DISC1
Luis Sanchez-Pulido1, Chris P Ponting
1Department of Physiology, Anatomy and Genetics, MRC Functional Genomics Unit, University of Oxford, South Parks Road, Oxford, UK.
Human Molecular Genetics
|August 20, 2011
Summary
The disrupted in schizophrenia 1 (DISC1) protein, linked to psychiatric disorders, is found across diverse eukaryotes, enabling new research models. Its structure reveals UVR-like repeats, aiding functional region identification.
Area of Science:
- Evolutionary biology
- Neuroscience
- Genetics
Background:
- The disrupted in schizophrenia 1 (DISC1) gene is associated with psychiatric conditions like schizophrenia, depression, and bipolar disorder.
- The evolutionary origin and structure of DISC1 have been challenging to study due to its rapid evolution and unusual composition.
- Understanding DISC1's evolutionary and structural basis is crucial for insights into human cognition and psychiatric diseases.
Purpose of the Study:
- To investigate the evolutionary history and structural characteristics of the DISC1 protein.
- To identify DISC1 homologues in a broader range of eukaryotic organisms.
- To delineate the functional regions of the DISC1 protein based on its structure.
Main Methods:
- In-depth sequence analyses of DISC1.
- Comparative genomics to identify DISC1 orthologues across diverse species.
- Protein structure prediction based on sequence data.
Main Results:
- DISC1 orthologues were predicted in various eukaryotes, including early-branching animals, plants, and algae, but not in fungi, nematodes, or fruit flies.
- The study identified two to four sequence repeats in DISC1 orthologues.
- The first two repeats show similarity to UVR domains and are predicted to form antiparallel alpha-helices, not coiled coils.
Conclusions:
- DISC1 is widespread among eukaryotes, allowing functional studies in simpler model organisms.
- Structural analysis reveals UVR-like domains within DISC1 repeats, providing clues to its function.
- Missense variants like L607F are located within these domains, aiding in the delineation of DISC1's functional regions.
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