Binding of human SWI1 ARID domain to DNA without sequence specificity: A molecular dynamics study.
10.1007/s11596-015-1455-9
- Author:
Qian SUN
1
;
Tao ZHU
;
Chang-Yu WANG
;
Ding MA
Author Information
1. Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China, endeavor_forever@126.com.
- Publication Type:Journal Article
- MeSH:
Binding Sites;
DNA;
chemistry;
metabolism;
DNA-Binding Proteins;
chemistry;
metabolism;
Drosophila Proteins;
chemistry;
Homeodomain Proteins;
chemistry;
Humans;
Models, Molecular;
Molecular Docking Simulation;
Molecular Dynamics Simulation;
Nuclear Proteins;
chemistry;
Protein Structure, Tertiary;
Transcription Factors;
chemistry;
metabolism
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(4):469-476
- CountryChina
- Language:English
-
Abstract:
SWI1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich interaction domain family (ARID), and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because ARID1A/BAF250a (SWI1) subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.
