Trimeric structure and flexibility of the L1ORF1 protein in human L1 retrotransposition
| Autor: | Regina Büttner, Elena Khazina, Vincent Truffault, Murray Coles, Steffen Schmidt, Oliver Weichenrieder |
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| Rok vydání: | 2011 |
| Předmět: |
Genetics
Coiled coil Flexibility (engineering) Models Molecular Mutagenesis (molecular biology technique) RNA Proteins Retrotransposon RNA-binding protein Interspersed Repetitive Sequences Computational biology Biology Crystallography X-Ray Genome Protein Structure Tertiary Substrate Specificity Long Interspersed Nucleotide Elements Structural Biology Humans Molecular Biology Nuclear Magnetic Resonance Biomolecular |
| Zdroj: | Nature structuralmolecular biology. 18(9) |
| ISSN: | 1545-9985 |
| Popis: | The process by which mammalian L1 retrotransposons move around the genome is not entirely clear. Now structural work on L1ORF1 protein, an RNA-binding protein essential for retrotransposition, reveals a trimeric organization and considerable interdomain flexibility. The latter is shown by mutagenesis to be critical for retrotransposition. The LINE-1 (L1) retrotransposon emerges as a major source of human interindividual genetic variation, with important implications for evolution and disease. L1 retrotransposition is poorly understood at the molecular level, and the mechanistic details and evolutionary origin of the L1-encoded L1ORF1 protein (L1ORF1p) are particularly obscure. Here three crystal structures of trimeric L1ORF1p and NMR solution structures of individual domains reveal a sophisticated and highly structured, yet remarkably flexible, RNA-packaging protein. It trimerizes via an N-terminal, ion-containing coiled coil that serves as scaffold for the flexible attachment of the central RRM and the C-terminal CTD domains. The structures explain the specificity for single-stranded RNA substrates, and a mutational analysis indicates that the precise control of domain flexibility is critical for retrotransposition. Although the evolutionary origin of L1ORF1p remains unclear, our data reveal previously undetected structural and functional parallels to viral proteins. |
| Databáze: | OpenAIRE |
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