Abstract
The PU.1 transcription factor is a member of the Ets family of DNA binding proteins. PU.1 binds to DNA via a loop-helix-loop domain and functions in the differentiation of hematopoietic cells. The structure of a PU.1-DNA complex was recently reported (Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R., and Ely, K. (1996) Nature 380, 456-460). The DNA in this complex is deformed by 8°as it curves around the protein. The pattern of electrostatic contacts between PU.1, and its DNA binding site suggests that laterally asymmetric phosphate neutralization accompanies PU.1 binding. Because of our previous studies showing that such neutralization can induce bending in naked DNA, we have explored the effect of phosphate neutralization by substituting neutral methylphosphonate internucleoside linkages at relevant positions within DNA containing the PU.1 binding sequence. Consistent with the prediction that DNA will collapse toward its partially neutralized surface, DNA neutralized at seven positions to simulate PU.1 binding is observed to bend by 28°. The directions of DNA curvature are slightly different in the co-crystal versus the partially neutralized duplexes. The electrostatic component of the binding energy appears more than enough to account for the DNA bending observed in the PU.1- DNA complex.
| Original language | English |
|---|---|
| Pages (from-to) | 31570-31575 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 272 |
| Issue number | 50 |
| DOIs | |
| State | Published - Dec 12 1997 |
| Externally published | Yes |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry
Cite this
Role of asymmetric phosphate neutralization in DNA bending by PU.1. / Strauss-Soukup, Juliane K.; Maher, L. James.
In: Journal of Biological Chemistry, Vol. 272, No. 50, 12.12.1997, p. 31570-31575.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of asymmetric phosphate neutralization in DNA bending by PU.1
AU - Strauss-Soukup, Juliane K.
AU - Maher, L. James
PY - 1997/12/12
Y1 - 1997/12/12
N2 - The PU.1 transcription factor is a member of the Ets family of DNA binding proteins. PU.1 binds to DNA via a loop-helix-loop domain and functions in the differentiation of hematopoietic cells. The structure of a PU.1-DNA complex was recently reported (Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R., and Ely, K. (1996) Nature 380, 456-460). The DNA in this complex is deformed by 8°as it curves around the protein. The pattern of electrostatic contacts between PU.1, and its DNA binding site suggests that laterally asymmetric phosphate neutralization accompanies PU.1 binding. Because of our previous studies showing that such neutralization can induce bending in naked DNA, we have explored the effect of phosphate neutralization by substituting neutral methylphosphonate internucleoside linkages at relevant positions within DNA containing the PU.1 binding sequence. Consistent with the prediction that DNA will collapse toward its partially neutralized surface, DNA neutralized at seven positions to simulate PU.1 binding is observed to bend by 28°. The directions of DNA curvature are slightly different in the co-crystal versus the partially neutralized duplexes. The electrostatic component of the binding energy appears more than enough to account for the DNA bending observed in the PU.1- DNA complex.
AB - The PU.1 transcription factor is a member of the Ets family of DNA binding proteins. PU.1 binds to DNA via a loop-helix-loop domain and functions in the differentiation of hematopoietic cells. The structure of a PU.1-DNA complex was recently reported (Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R., and Ely, K. (1996) Nature 380, 456-460). The DNA in this complex is deformed by 8°as it curves around the protein. The pattern of electrostatic contacts between PU.1, and its DNA binding site suggests that laterally asymmetric phosphate neutralization accompanies PU.1 binding. Because of our previous studies showing that such neutralization can induce bending in naked DNA, we have explored the effect of phosphate neutralization by substituting neutral methylphosphonate internucleoside linkages at relevant positions within DNA containing the PU.1 binding sequence. Consistent with the prediction that DNA will collapse toward its partially neutralized surface, DNA neutralized at seven positions to simulate PU.1 binding is observed to bend by 28°. The directions of DNA curvature are slightly different in the co-crystal versus the partially neutralized duplexes. The electrostatic component of the binding energy appears more than enough to account for the DNA bending observed in the PU.1- DNA complex.
UR - http://www.scopus.com/inward/record.url?scp=0031452012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031452012&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.50.31570
DO - 10.1074/jbc.272.50.31570
M3 - Article
C2 - 9395494
AN - SCOPUS:0031452012
VL - 272
SP - 31570
EP - 31575
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 50
ER -