Summary information and primary citation
- PDB-id
-
3oqo;
DSSR-derived features in text and
JSON formats
- Class
- transcription-transferase-DNA
- Method
- X-ray (2.97 Å)
- Summary
- Ccpa-hpr-ser46p-syn cre
- Reference
-
Schumacher MA, Sprehe M, Bartholomae M, Hillen W, Brennan
RG (2011): "Structures
of carbon catabolite protein A-(HPr-Ser46-P) bound to
diverse catabolite response element sites reveal the
basis for high-affinity binding to degenerate DNA
operators." Nucleic Acids Res.,
39, 2931-2942. doi: 10.1093/nar/gkq1177.
- Abstract
- In Gram-positive bacteria, carbon catabolite protein A
(CcpA) is the master regulator of carbon catabolite
control, which ensures optimal energy usage under diverse
conditions. Unlike other LacI-GalR proteins, CcpA is
activated for DNA binding by first forming a complex with
the phosphoprotein HPr-Ser46-P. Bacillus subtilis CcpA
functions as both a transcription repressor and activator
and binds to more than 50 operators called catabolite
response elements (cres). These sites are highly degenerate
with the consensus, WTGNNARCGNWWWCAW. How
CcpA-(HPr-Ser46-P) binds such diverse sequences is unclear.
To gain insight into this question, we solved the
structures of the CcpA-(HPr-Ser46-P) complex bound to three
different operators, the synthetic (syn) cre, ackA2 cre and
gntR-down cre. Strikingly, the structures show that the
CcpA-bound operators display different bend angles, ranging
from 31° to 56°. These differences are accommodated by a
flexible linkage between the CcpA
helix-turn-helix-loop-helix motif and hinge helices, which
allows independent docking of these DNA-binding modules.
This flexibility coupled with an abundance of non-polar
residues capable of non-specific nucleobase interactions
permits CcpA-(HPr-Ser46-P) to bind diverse operators.
Indeed, biochemical data show that CcpA-(HPr-Ser46-P) binds
the three cre sites with similar affinities. Thus, the data
reveal properties that license this protein to function as
a global transcription regulator.
