Abstract
Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. However, the mechanistic basis underlying this extended repertoire has remained largely unexplored. In this study, we used an extensive set of mutations to demonstrate that Campylobacter jejuni Fur (CjFur) employs the same surface to positively and negatively control gene expression regardless of the presence or absence of metals. Moreover, the crystal structure determination of a CjFur devoid of any regulatory metals shows that subtle reorientation of the transcription factor DNA binding domain negatively impacts DNA binding, gene expression and gut colonization in chickens. Overall, these results highlight the versatility of the CjFur DNA binding domain in mediating all gene regulatory events controlled by the metalloregulator and that the full metalation of CjFur is critical to the Campylobacter jejuni life cycle in vivo.
| Original language | English (US) |
|---|---|
| Article number | 7140 |
| Journal | Scientific reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators. / Sarvan, Sabina; Charih, François; Askoura, Momen; Butcher, James; Brunzelle, Joseph S; Stintzi, Alain; Couture, Jean François.
In: Scientific reports, Vol. 8, No. 1, 7140, 01.12.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Functional insights into the interplay between DNA interaction and metal coordination in ferric uptake regulators
AU - Sarvan, Sabina
AU - Charih, François
AU - Askoura, Momen
AU - Butcher, James
AU - Brunzelle, Joseph S
AU - Stintzi, Alain
AU - Couture, Jean François
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. However, the mechanistic basis underlying this extended repertoire has remained largely unexplored. In this study, we used an extensive set of mutations to demonstrate that Campylobacter jejuni Fur (CjFur) employs the same surface to positively and negatively control gene expression regardless of the presence or absence of metals. Moreover, the crystal structure determination of a CjFur devoid of any regulatory metals shows that subtle reorientation of the transcription factor DNA binding domain negatively impacts DNA binding, gene expression and gut colonization in chickens. Overall, these results highlight the versatility of the CjFur DNA binding domain in mediating all gene regulatory events controlled by the metalloregulator and that the full metalation of CjFur is critical to the Campylobacter jejuni life cycle in vivo.
AB - Ferric uptake regulators (Fur) are a family of transcription factors coupling gene regulatory events to metal concentration. Recent evidence has expanded the mechanistic repertoires employed by Fur to activate or repress gene expression in the presence or absence of regulatory metals. However, the mechanistic basis underlying this extended repertoire has remained largely unexplored. In this study, we used an extensive set of mutations to demonstrate that Campylobacter jejuni Fur (CjFur) employs the same surface to positively and negatively control gene expression regardless of the presence or absence of metals. Moreover, the crystal structure determination of a CjFur devoid of any regulatory metals shows that subtle reorientation of the transcription factor DNA binding domain negatively impacts DNA binding, gene expression and gut colonization in chickens. Overall, these results highlight the versatility of the CjFur DNA binding domain in mediating all gene regulatory events controlled by the metalloregulator and that the full metalation of CjFur is critical to the Campylobacter jejuni life cycle in vivo.
UR - http://www.scopus.com/inward/record.url?scp=85046876567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046876567&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-25157-6
DO - 10.1038/s41598-018-25157-6
M3 - Article
C2 - 29739988
AN - SCOPUS:85046876567
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 7140
ER -