Signatures of protein-DNA recognition in free DNA binding sites.
One obstacle to achieving complete understanding of the principles underlying sequence-dependent recognition of DNA is the paucity of structural data for DNA recognition sequences in their free (unbound) state. Here, we carried out crystallization screening of 50 DNA duplexes containing cognate protein binding sites and obtained new crystal structures of free DNA binding sites for three distinct modes of DNA recognition: anti-parallel beta strands (MetR), helix-turn-helix motif + hinge helices (PurR), and zinc fingers (Zif268). Structural changes between free and protein-bound DNA are manifested differently in each case. The new DNA structures reveal that distinctive sequence-dependent DNA geometry dominates recognition by MetR, protein-induced bending of DNA dictates recognition by PurR, and deformability of DNA along the A-B continuum is important in recognition by Zif268. Together, our findings show that crystal structures of free DNA binding sites provide new information about the nature of protein-DNA interactions and thus lend insights towards a structural code for DNA recognition.
Locasale
Jason W
JW
Department of Chemistry and Chemical Biology, Rutgers, State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA. cathy.lawson@rutgers.edu
Napoli
Andrew A
AA
Chen
Shengfeng
S
Berman
Helen M
HM
Lawson
Catherine L
CL
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D016335:Zinc Fingers
D001426:Bacterial Proteins; D051766:Early Growth Response Protein 1; D011506:Proteins; C065825:PurR protein, Bacteria; D012097:Repressor Proteins; C060486:methionine repressor protein, Bacteria; D004247:DNA