Structure specific recognition protein-1 (SSRP1) is an elongated homodimer that binds histones

Marciano, G., Da Vela, S., Tria, G., Svergun, D. I., Byron, O. and Huang, D. T. (2018) Structure specific recognition protein-1 (SSRP1) is an elongated homodimer that binds histones. Journal of Biological Chemistry, 293(26), pp. 10071-10083. (doi:10.1074/jbc.RA117.000994) (PMID:29764934)

Marciano, G., Da Vela, S., Tria, G., Svergun, D. I., Byron, O. and Huang, D. T. (2018) Structure specific recognition protein-1 (SSRP1) is an elongated homodimer that binds histones. Journal of Biological Chemistry, 293(26), pp. 10071-10083. (doi:10.1074/jbc.RA117.000994) (PMID:29764934)

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Abstract

The histone chaperone complex facilitates chromatin transcription (FACT) plays important roles in DNA repair, replication, and transcription. In the formation of this complex, structure-specific recognition protein-1 (SSRP1) heterodimerizes with suppressor of Ty 16 (SPT16). SSRP1 also has SPT16-independent functions, but how SSRP1 functions alone remains elusive. Here, using analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS) techniques, we characterized human SSRP1 and that from the amoeba Dictyostelium discoideum and show that both orthologs form an elongated homodimer in solution. We found that substitutions in the SSRP1 pleckstrin homology domain known to bind SPT16 also disrupt SSRP1 homodimerization. Moreover, AUC and SAXS analyses revealed that SSRP1 homodimerization and heterodimerization with SPT16 (resulting in FACT) involve the same SSRP1 surface, namely, the PH2 region, and that the FACT complex contains only one molecule of SSRP1. These observations suggest that SSRP1 homo- and heterodimerization might be mutually exclusive. Moreover, isothermal titration calorimetry analyses disclosed that SSRP1 binds both histones H2A-H2B and H3-H4 and that disruption of SSRP1 homodimerization decreases its histone-binding affinity. Together, our results provide evidence for regulation of SSRP1 by homodimerization and suggest a potential role for homodimerization in facilitating SPT16-independent functions of SSRP1.

Item Type:Articles
Keywords:H2A-H2B, H3-H4, SSRP1, analytical ultracentrifugation, histone, histone chaperone, homodimer, oligomerization, small-angle X-ray scattering (SAXS).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Byron, Professor Olwyn and Marciano, Mr Gabriele and Huang, Dr Danny
Authors: Marciano, G., Da Vela, S., Tria, G., Svergun, D. I., Byron, O., and Huang, D. T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:15 May 2018
Copyright Holders:Copyright © 2018 The American Society for Biochemistry and Molecular Biology, Inc.
First Published:First published in Journal of Biological Chemistry 293(26): 10071-10083
Publisher Policy:Reproduced under a Creative Commons License

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