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The AibR-isovaleryl coenzyme A regulator and its DNA binding site - a model for the regulation of alternative de novo isovaleryl coenzyme A biosynthesis in Myxococcus xanthus.

Bock, Tobias
; 
Volz, Carsten
; 
Hering, Vanessa
; 
Scrima, Andrea
; 
Müller, Rolf
; 
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2016-12-09
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Abstract
Isovaleryl coenzyme A (IV-CoA) is an important building block of iso-fatty acids. In myxobacteria, IV-CoA is essential for the formation of signaling molecules involved in fruiting body formation. Leucine degradation is the common source of IV-CoA, but a second, de novo biosynthetic route to IV-CoA termed AIB (alternative IV-CoA biosynthesis) was recently discovered in M. xanthus The AIB-operon contains the TetR-like transcriptional regulator AibR, which we characterize in this study. We demonstrate that IV-CoA binds AibR with micromolar affinity and show by gelshift experiments that AibR interacts with the promoter region of the AIB-operon once IV-CoA is present. We identify an 18-bp near-perfect palindromic repeat as containing the AibR operator and provide evidence that AibR also controls an additional genomic locus coding for a putative acetyl-CoA acetyltransferase. To elucidate atomic details, we determined crystal structures of AibR in the apo, the IV-CoA- and the IV-CoA-DNA-bound state to 1.7 Å, 2.35 Å and 2.92 Å, respectively. IV-CoA induces partial unfolding of an α-helix, which allows sequence-specific interactions between AibR and its operator. This study provides insights into AibR-mediated regulation and shows that AibR functions in an unusual TetR-like manner by blocking transcription not in the ligand-free but in the effector-bound state.
Citation
The AibR-isovaleryl coenzyme A regulator and its DNA binding site - a model for the regulation of alternative de novo isovaleryl coenzyme A biosynthesis in Myxococcus xanthus. 2016 Nucleic Acids Res.
Affiliation
Hel,holtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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Nucleic acids research
URI
http://hdl.handle.net/10033/620688
DOI
10.1093/nar/gkw1238
PubMed ID
27940564
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Language
en
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1362-4962
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Publications of the research group structure and functions of Proteins(SFPR)
publications of the research group of microbial natural substances([HIPS]MINS)
research group of structural biology of autophagy (SBAU)