2rhx: Difference between revisions

Revision as of 19:47, 21 February 2008

Crystal structure of the 3-MBT repeats from human L3MBTL1 bound to dimethyl-lysine

OverviewOverview

Human L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds monomethylated and dimethylated lysines, but not trimethylated lysines, in several histone sequence contexts. In crystal structures of L3MBTL1 complexes, the monomethyl- and dimethyllysines insert into a narrow and deep cavity of aromatic residue-lined pocket 2, while a proline ring inserts into shallower pocket 1. We have also engineered a single Y to E substitution within the aromatic cage of the BPTF PHD finger, resulting in a reversal of binding preference from trimethyl- to dimethyllysine in an H3K4 sequence context. In both the "cavity insertion" (L3MBTL1) and "surface groove" (PHD finger) modes of methyllysine recognition, a carboxylate group both hydrogen bonds and ion pairs to the methylammonium proton. Our structural and binding studies of these two modules provide insights into the molecular principles governing the decoding of lysine methylation states, thereby highlighting a methylation state-specific layer of histone mark readout impacting on epigenetic regulation.

About this StructureAbout this Structure

2RHX is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger., Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, Patel DJ, Mol Cell. 2007 Nov 30;28(4):677-91. PMID:18042461

Page seeded by OCA on Thu Feb 21 18:47:24 2008

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OCA

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 ==Overview==
-Human L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds monomethylated and dimethylated lysines, but not trimethylated, lysines, in several histone sequence contexts. In crystal structures of, L3MBTL1 complexes, the monomethyl- and dimethyllysines insert into a, narrow and deep cavity of aromatic residue-lined pocket 2, while a proline, ring inserts into shallower pocket 1. We have also engineered a single Y, to E substitution within the aromatic cage of the BPTF PHD finger, resulting in a reversal of binding preference from trimethyl- to, dimethyllysine in an H3K4 sequence context. In both the "cavity insertion", (L3MBTL1) and "surface groove" (PHD finger) modes of methyllysine, recognition, a carboxylate group both hydrogen bonds and ion pairs to the, methylammonium proton. Our structural and binding studies of these two, modules provide insights into the molecular principles governing the, decoding of lysine methylation states, thereby highlighting a methylation, state-specific layer of histone mark readout impacting on epigenetic, regulation.
+Human L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds monomethylated and dimethylated lysines, but not trimethylated lysines, in several histone sequence contexts. In crystal structures of L3MBTL1 complexes, the monomethyl- and dimethyllysines insert into a narrow and deep cavity of aromatic residue-lined pocket 2, while a proline ring inserts into shallower pocket 1. We have also engineered a single Y to E substitution within the aromatic cage of the BPTF PHD finger, resulting in a reversal of binding preference from trimethyl- to dimethyllysine in an H3K4 sequence context. In both the "cavity insertion" (L3MBTL1) and "surface groove" (PHD finger) modes of methyllysine recognition, a carboxylate group both hydrogen bonds and ion pairs to the methylammonium proton. Our structural and binding studies of these two modules provide insights into the molecular principles governing the decoding of lysine methylation states, thereby highlighting a methylation state-specific layer of histone mark readout impacting on epigenetic regulation.
 ==About this Structure==
@@ Line 10: / Line 10: @@
 ==Reference==
-Structural Basis for Lower Lysine Methylation State-Specific Readout by MBT Repeats of L3MBTL1 and an Engineered PHD Finger., Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, Patel DJ, Mol Cell. 2007 Nov 30;28(4):677-91. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042461 18042461]
+Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger., Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, Patel DJ, Mol Cell. 2007 Nov 30;28(4):677-91. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042461 18042461]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
 [[Category: Li, H.]]
-[[Category: Patel, D.J.]]
+[[Category: Patel, D J.]]
 [[Category: MLY]]
 [[Category: PG4]]
@@ Line 32: / Line 32: @@
 [[Category: zinc-finger]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:45:42 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:47:24 2008''