Structure and DNA-binding sites of the SWI1 AT-rich interaction domain (ARID) suggest determinants for sequence-specific DNA recognition.
ARID (AT-rich interaction domain) is a homologous family of DNA-binding domains that occur in DNA-binding proteins from a wide variety of species, ranging from yeast to nematodes, insects, mammals, and plants. SWI1, a member of the SWI/SNF protein complex that is involved in chromatin remodeling during transcription, contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does not select for a specific DNA sequence from a random sequence pool. The lack of sequence specificity shown by the SWI1 ARID domain stands in contrast to the other characterized ARID domains, which recognize specific AT-rich sequences. We have solved the three-dimensional structure of human SWI1 ARID using solution NMR methods. In addition, we have characterized nonspecific DNA binding by the SWI1 ARID domain. Results from this study indicate that a flexible, long, internal loop in the ARID motif is likely to be important for sequence-specific DNA recognition. The structure of the human SWI1 ARID domain also represents a distinct structural subfamily. Studies of ARID indicate that the boundary of DNA binding structural and functional domains can extend beyond the sequence homologous region in a homologous family of proteins. Structural studies of homologous domains such as the ARID family of DNA-binding domains should provide information to better predict the boundary of structural and functional domains in structural genomic studies.
Kim
Suhkmann
S
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Zhang
Ziming
Z
Upchurch
Sean
S
Isern
Nancy
N
Chen
Yuan
Y
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA