Work

L1 retrotransposition requires rapid ORF1p oligomerization, a novel coiled coil-dependent property conserved despite extensive remodeling

Year: 2015

Type: article

Abstract: Detailed mechanistic understanding of L1 retrotransposition is sparse, particularly with respect to ORF1p, a coiled coil-mediated homotrimeric nucleic acid chaperone that can form tightly packed oligomers on nucleic acids. Although the coiled coil motif is highly conserved, it is uniquely susceptible to evolutionary change. Here we studied three ORF1 proteins: a modern human one (111p), its resuscitated primate ancestor (555p) and a mosaic modern protein (151p) wherein 9 of the 30 coiled coil substitutions retain their ancestral state. While 111p and 555p equally supported retrotransposition, 151p was inactive. Nonetheless, they were fully active in bulk assays of nucleic acid interactions including chaperone activity. However, single molecule assays showed that 151p trimers form stably bound oligomers on ssDNA at <1/10th the rate of the active proteins, revealing that oligomerization rate is a novel critical parameter of ORF1p activity in retrotransposition conserved for at least the last 25 Myr of primate evolution.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkv1342

Authors: M. Nabuan Naufer, Kathryn E. Callahan, Pamela R. Cook, Cesar E. Perez-Gonzalez, Mark C. Williams, Anthony V. Furano

Institutions: Northeastern University, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

Language: English

Topic: Chromosomal and Genetic Variations

Subfield: Plant Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funders: National Institutes of Health, U.S. Public Health Service, National Institute of General Medical Sciences