2l92
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
[[2l92]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Burkholderia_vietnamiensis Burkholderia vietnamiensis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L92 OCA]. <br> | [[2l92]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Burkholderia_vietnamiensis Burkholderia vietnamiensis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L92 OCA]. <br> | ||
| - | <b>Related:</b> [[2l93|2l93]]<br> | + | <b>[[Related_structure|Related:]]</b> [[2l93|2l93]]<br> |
<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | ||
| + | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l92 RCSB], [http://www.ebi.ac.uk/pdbsum/2l92 PDBsum]</span><br> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
H-NS and Lsr2 are nucleoid-associated proteins from Gram-negative bacteria and Mycobacteria, respectively, that play an important role in the silencing of horizontally acquired foreign DNA that is more AT-rich than the resident genome. Despite the fact that Lsr2 and H-NS proteins are dissimilar in sequence and structure, they serve apparently similar functions and can functionally complement one another. The mechanism by which these xenogeneic silencers selectively target AT-rich DNA has been enigmatic. We performed high-resolution protein binding microarray analysis to simultaneously assess the binding preference of H-NS and Lsr2 for all possible 8-base sequences. Concurrently, we performed a detailed structure-function relationship analysis of their C-terminal DNA binding domains by NMR. Unexpectedly, we found that H-NS and Lsr2 use a common DNA binding mechanism where a short loop containing a "Q/RGR" motif selectively interacts with the DNA minor groove, where the highest affinity is for AT-rich sequences that lack A-tracts. Mutations of the Q/RGR motif abolished DNA binding activity. Netropsin, a DNA minor groove-binding molecule effectively outcompeted H-NS and Lsr2 for binding to AT-rich sequences. These results provide a unified molecular mechanism to explain findings related to xenogeneic silencing proteins, including their lack of apparent sequence specificity but preference for AT-rich sequences. Our findings also suggest that structural information contained within the DNA minor groove is deciphered by xenogeneic silencing proteins to distinguish genetic material that is self from nonself. | H-NS and Lsr2 are nucleoid-associated proteins from Gram-negative bacteria and Mycobacteria, respectively, that play an important role in the silencing of horizontally acquired foreign DNA that is more AT-rich than the resident genome. Despite the fact that Lsr2 and H-NS proteins are dissimilar in sequence and structure, they serve apparently similar functions and can functionally complement one another. The mechanism by which these xenogeneic silencers selectively target AT-rich DNA has been enigmatic. We performed high-resolution protein binding microarray analysis to simultaneously assess the binding preference of H-NS and Lsr2 for all possible 8-base sequences. Concurrently, we performed a detailed structure-function relationship analysis of their C-terminal DNA binding domains by NMR. Unexpectedly, we found that H-NS and Lsr2 use a common DNA binding mechanism where a short loop containing a "Q/RGR" motif selectively interacts with the DNA minor groove, where the highest affinity is for AT-rich sequences that lack A-tracts. Mutations of the Q/RGR motif abolished DNA binding activity. Netropsin, a DNA minor groove-binding molecule effectively outcompeted H-NS and Lsr2 for binding to AT-rich sequences. These results provide a unified molecular mechanism to explain findings related to xenogeneic silencing proteins, including their lack of apparent sequence specificity but preference for AT-rich sequences. Our findings also suggest that structural information contained within the DNA minor groove is deciphered by xenogeneic silencing proteins to distinguish genetic material that is self from nonself. | ||
Revision as of 10:17, 30 April 2014
Solution structure of the C-terminal domain of H-NS like protein Bv3F
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