Hodson, C., Cole, A. R., Lewis, L. P. C., Miles, J. A., Purkiss, A. and Walden, H. (2011) Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway. Journal of Biological Chemistry, 286(37), pp. 32628-32637. (doi: 10.1074/jbc.M111.244632) (PMID:21775430) (PMCID:PMC3173227)
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Abstract
The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand cross-links. At the heart of this pathway is the monoubiquitination of the FANCI-FANCD2 (ID) complex by the multiprotein “core complex” containing the E3 ubiquitin ligase FANCL. Vertebrate organisms have the eight-protein core complex, whereas invertebrates apparently do not. We report here the structure of the central domain of human FANCL in comparison with the recently solved Drosophila melanogaster FANCL. Our data represent the first structural detail into the catalytic core of the human system and reveal that the central fold of FANCL is conserved between species. However, there are macromolecular differences between the FANCL proteins that may account for the apparent distinctions in core complex requirements between the vertebrate and invertebrate FA pathways. In addition, we characterize the binding of human FANCL with its partners, Ube2t, FANCD2, and FANCI. Mutational analysis reveals which residues are required for substrate binding, and we also show the domain required for E2 binding.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Walden, Professor Helen |
| Authors: | Hodson, C., Cole, A. R., Lewis, L. P. C., Miles, J. A., Purkiss, A., and Walden, H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Journal of Biological Chemistry |
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0021-9258 |
| ISSN (Online): | 1083-351X |
| Published Online: | 20 July 2011 |
| Copyright Holders: | Copyright © 2017 The Authors1 |
| First Published: | First published in Journal of Biological Chemistry 286(37):32628-32637 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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