The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]

Publication Date:
2018-12-15
Publisher:
The American Society for Biochemistry and Molecular Biology (ASBMB)
Print ISSN:
0021-9258
Electronic ISSN:
1083-351X
Topics:
Biology
Chemistry and Pharmacology
Published by:
http://www.asbmb.org/
_version_ 1836399105574699008
autor Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
beschreibung Toxin–antitoxin (TA) systems are present in many bacteria and play important roles in bacterial growth, physiology, and pathogenicity. Those that are best studied are the type II TA systems, in which both toxins and antitoxins are proteins. The HicAB system is one of the prototypic TA systems, found in many bacterial species. Complex interactions between the protein toxin (HicA), the protein antitoxin (HicB), and the DNA upstream of the encoding genes regulate the activity of this system, but few structural details are available about how HicA destabilizes the HicB–DNA complex. Here, we determined the X-ray structures of HicB and the HicAB complex to 1.8 and 2.5 Å resolution, respectively, and characterized their DNA interactions. This revealed that HicB forms a tetramer and HicA and HicB form a heterooctameric complex that involves structural reorganization of the C-terminal (DNA-binding) region of HicB. Our observations indicated that HicA has a profound impact on binding of HicB to DNA sequences upstream of hicAB in a stoichiometric-dependent way. At low ratios of HicA:HicB, there was no effect on DNA binding, but at higher ratios, the affinity for DNA declined cooperatively, driving dissociation of the HicA:HicB:DNA complex. These results reveal the structural mechanisms by which HicA de-represses the HicB–DNA complex.
citation_standardnr 6369920
datenlieferant ipn_articles
feed_id 43
feed_publisher The American Society for Biochemistry and Molecular Biology (ASBMB)
feed_publisher_url http://www.asbmb.org/
insertion_date 2018-12-15
journaleissn 1083-351X
journalissn 0021-9258
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Biochemistry and Molecular Biology (ASBMB)
quelle Journal of Biological Chemistry
relation http://feedproxy.google.com/~r/jbc/SUcv/~3/kGSgD0SsETI/19429.short
search_space articles
shingle_author_1 Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
shingle_author_2 Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
shingle_author_3 Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
shingle_author_4 Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
shingle_catch_all_1 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
Toxin–antitoxin (TA) systems are present in many bacteria and play important roles in bacterial growth, physiology, and pathogenicity. Those that are best studied are the type II TA systems, in which both toxins and antitoxins are proteins. The HicAB system is one of the prototypic TA systems, found in many bacterial species. Complex interactions between the protein toxin (HicA), the protein antitoxin (HicB), and the DNA upstream of the encoding genes regulate the activity of this system, but few structural details are available about how HicA destabilizes the HicB–DNA complex. Here, we determined the X-ray structures of HicB and the HicAB complex to 1.8 and 2.5 Å resolution, respectively, and characterized their DNA interactions. This revealed that HicB forms a tetramer and HicA and HicB form a heterooctameric complex that involves structural reorganization of the C-terminal (DNA-binding) region of HicB. Our observations indicated that HicA has a profound impact on binding of HicB to DNA sequences upstream of hicAB in a stoichiometric-dependent way. At low ratios of HicA:HicB, there was no effect on DNA binding, but at higher ratios, the affinity for DNA declined cooperatively, driving dissociation of the HicA:HicB:DNA complex. These results reveal the structural mechanisms by which HicA de-represses the HicB–DNA complex.
Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_2 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
Toxin–antitoxin (TA) systems are present in many bacteria and play important roles in bacterial growth, physiology, and pathogenicity. Those that are best studied are the type II TA systems, in which both toxins and antitoxins are proteins. The HicAB system is one of the prototypic TA systems, found in many bacterial species. Complex interactions between the protein toxin (HicA), the protein antitoxin (HicB), and the DNA upstream of the encoding genes regulate the activity of this system, but few structural details are available about how HicA destabilizes the HicB–DNA complex. Here, we determined the X-ray structures of HicB and the HicAB complex to 1.8 and 2.5 Å resolution, respectively, and characterized their DNA interactions. This revealed that HicB forms a tetramer and HicA and HicB form a heterooctameric complex that involves structural reorganization of the C-terminal (DNA-binding) region of HicB. Our observations indicated that HicA has a profound impact on binding of HicB to DNA sequences upstream of hicAB in a stoichiometric-dependent way. At low ratios of HicA:HicB, there was no effect on DNA binding, but at higher ratios, the affinity for DNA declined cooperatively, driving dissociation of the HicA:HicB:DNA complex. These results reveal the structural mechanisms by which HicA de-represses the HicB–DNA complex.
Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_3 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
Toxin–antitoxin (TA) systems are present in many bacteria and play important roles in bacterial growth, physiology, and pathogenicity. Those that are best studied are the type II TA systems, in which both toxins and antitoxins are proteins. The HicAB system is one of the prototypic TA systems, found in many bacterial species. Complex interactions between the protein toxin (HicA), the protein antitoxin (HicB), and the DNA upstream of the encoding genes regulate the activity of this system, but few structural details are available about how HicA destabilizes the HicB–DNA complex. Here, we determined the X-ray structures of HicB and the HicAB complex to 1.8 and 2.5 Å resolution, respectively, and characterized their DNA interactions. This revealed that HicB forms a tetramer and HicA and HicB form a heterooctameric complex that involves structural reorganization of the C-terminal (DNA-binding) region of HicB. Our observations indicated that HicA has a profound impact on binding of HicB to DNA sequences upstream of hicAB in a stoichiometric-dependent way. At low ratios of HicA:HicB, there was no effect on DNA binding, but at higher ratios, the affinity for DNA declined cooperatively, driving dissociation of the HicA:HicB:DNA complex. These results reveal the structural mechanisms by which HicA de-represses the HicB–DNA complex.
Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_4 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
Toxin–antitoxin (TA) systems are present in many bacteria and play important roles in bacterial growth, physiology, and pathogenicity. Those that are best studied are the type II TA systems, in which both toxins and antitoxins are proteins. The HicAB system is one of the prototypic TA systems, found in many bacterial species. Complex interactions between the protein toxin (HicA), the protein antitoxin (HicB), and the DNA upstream of the encoding genes regulate the activity of this system, but few structural details are available about how HicA destabilizes the HicB–DNA complex. Here, we determined the X-ray structures of HicB and the HicAB complex to 1.8 and 2.5 Å resolution, respectively, and characterized their DNA interactions. This revealed that HicB forms a tetramer and HicA and HicB form a heterooctameric complex that involves structural reorganization of the C-terminal (DNA-binding) region of HicB. Our observations indicated that HicA has a profound impact on binding of HicB to DNA sequences upstream of hicAB in a stoichiometric-dependent way. At low ratios of HicA:HicB, there was no effect on DNA binding, but at higher ratios, the affinity for DNA declined cooperatively, driving dissociation of the HicA:HicB:DNA complex. These results reveal the structural mechanisms by which HicA de-represses the HicB–DNA complex.
Ashley J. Winter, Christopher Williams, Michail N. Isupov, Hannah Crocker, Mariya Gromova, Philip Marsh, Oliver J. Wilkinson, Mark S. Dillingham, Nicholas J. Harmer, Richard W. Titball, Matthew P. Crump
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_title_1 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
shingle_title_2 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
shingle_title_3 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
shingle_title_4 The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
timestamp 2025-06-30T23:37:41.422Z
titel The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
titel_suche The molecular basis of protein toxin HicA-dependent binding of the protein antitoxin HicB to DNA [Protein Structure and Folding]
topic W
V
uid ipn_articles_6369920