Structural basis of hAT transposon end recognition by Hermes, an octameric DNA transposase from Musca domestica

Alison B Hickman; Hosam E Ewis; Xianghong Li; Joshua A Knapp; Thomas Laver; Anna-Louise Doss; Gökhan Tolun; Alasdair C Steven; Alexander Grishaev; Ad Bax; Peter W Atkinson; Nancy L Craig; Fred Dyda

doi:10.1016/j.cell.2014.05.037

Structural basis of hAT transposon end recognition by Hermes, an octameric DNA transposase from Musca domestica

Cell. 2014 Jul 17;158(2):353-367. doi: 10.1016/j.cell.2014.05.037.

Authors

Affiliations

¹ Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
² Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Graduate Program in Biochemistry and Molecular Biology, University of California Riverside, Riverside, CA 92521, USA.
⁴ Graduate Program in Genetics, Genomics, and Bioinformatics, University of California Riverside, Riverside, CA 92521, USA.
⁵ Graduate Program in Cell, Molecular, and Developmental Biology, University of California Riverside, Riverside, CA 92521, USA.
⁶ Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Graduate Program in Biochemistry and Molecular Biology, University of California Riverside, Riverside, CA 92521, USA; Graduate Program in Genetics, Genomics, and Bioinformatics, University of California Riverside, Riverside, CA 92521, USA; Graduate Program in Cell, Molecular, and Developmental Biology, University of California Riverside, Riverside, CA 92521, USA; Department of Entomology and Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA 92521, USA.
⁹ Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: fred.dyda@nih.gov.

Abstract

Hermes is a member of the hAT transposon superfamily that has active representatives, including McClintock's archetypal Ac mobile genetic element, in many eukaryotic species. The crystal structure of the Hermes transposase-DNA complex reveals that Hermes forms an octameric ring organized as a tetramer of dimers. Although isolated dimers are active in vitro for all the chemical steps of transposition, only octamers are active in vivo. The octamer can provide not only multiple specific DNA-binding domains to recognize repeated subterminal sequences within the transposon ends, which are important for activity, but also multiple nonspecific DNA binding surfaces for target capture. The unusual assembly explains the basis of bipartite DNA recognition at hAT transposon ends, provides a rationale for transposon end asymmetry, and suggests how the avidity provided by multiple sites of interaction could allow a transposase to locate its transposon ends amidst a sea of chromosomal DNA.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Animals
Base Sequence
Crystallography, X-Ray
DNA Transposable Elements*
Dimerization
Houseflies / enzymology*
Houseflies / genetics
Insect Proteins / chemistry
Insect Proteins / genetics
Insect Proteins / metabolism
Models, Molecular
Molecular Sequence Data
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
Transposases / chemistry*
Transposases / genetics
Transposases / metabolism

Substances

DNA Transposable Elements
Insect Proteins
RNA-Binding Proteins
Transposases

Associated data

PDB/4D1Q

Grants and funding

Z01 DK036153-01/Intramural NIH HHS/United States