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Updated: Mar 28, 2026

Analyzing DNA-Protein Interactions with Streptavidin-Based Biolayer Interferometry
Published on: January 17, 2025
Crystal Structure of Human SSRP1 Middle Domain Reveals a Role in DNA Binding
Wenjuan Zhang1,2, Fuxing Zeng1,2, Yiwei Liu1,2
1Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Network, School of Life Science, 96 Jinzhai Road, Hefei, Anhui, 230026, People's Republic of China.
Abstract:
SSRP1 is a subunit of the FACT complex, an important histone chaperone required for transcriptional regulation, DNA replication and damage repair. SSRP1 also plays important roles in transcriptional regulation independent of Spt16 and interacts with other proteins. Here, we report the crystal structure of the middle domain of SSRP1. It consists of tandem pleckstrin homology (PH) domains. These domains differ from the typical PH domain in that PH1 domain has an extra conserved βαβ topology. SSRP1 contains the well-characterized DNA-binding HMG-1 domain. Our studies revealed that SSRP1-M can also participate in DNA binding, and that this binding involves one positively charged patch on the surface of the structure. In addition, SSRP1-M did not bind to histones, which was assessed through pull-down assays. This aspect makes the protein different from other related proteins adopting the double PH domain structure. Our studies facilitate the understanding of SSRP1 and provide insights into the molecular mechanisms of interaction with DNA and histones of the FACT complex.
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