PDBsum entry 2ri7

Transcription/nuclear protein

PDB id: 2ri7

Contents

Protein chain

168 a.a. *

Ligands

ALA-ARG-THR-MLY-GLN-THR

GOL

IPA

Metals

_ZN ×2

Waters ×337

* Residue conservation analysis

PDB id:

2ri7

Name:

Transcription/nuclear protein

Title:

Crystal structure of phd finger-linker-bromodomain y17e mutant from human bptf in the h3(1-9)k4me2 bound state

Structure:

Nucleosome-remodeling factor subunit bptf. Chain: a. Fragment: phd-type 2 domain and bromo domain. Residues 2726-2894. Synonym: bromodomain and phd finger- containing transcription factor, fetal alzheimer antigen, fetal alz- 50 clone 1 protein. Engineered: yes. Mutation: yes. Histone h3.1. Chain: p.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bptf, fac1, falz. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans

Resolution:

1.45Å R-factor: 0.189 R-free: 0.192

Authors:

H.Li,D.J.Patel

Key ref:

H.Li et al. (2007). Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Mol Cell, 28, 677-691. PubMed id: 18042461 DOI: 10.1016/j.molcel.2007.10.023

Date:

10-Oct-07 Release date: 11-Dec-07

Protein chain

Q12830  (BPTF_HUMAN) -  Nucleosome-remodeling factor subunit BPTF from Homo sapiens

Seq: 3046 a.a.

Struc: 168 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.molcel.2007.10.023

Mol Cell 28:677-691 (2007)

PubMed id: 18042461

Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger.

H.Li, W.Fischle, W.Wang, E.M.Duncan, L.Liang, S.Murakami-Ishibe, C.D.Allis, D.J.Patel.

ABSTRACT

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.

Selected figure(s)

Figure 2.
Figure 2. Pro-Ser Step-Containing Peptide Binding by L3MBTL1 Pocket 1
(A) Domain architecture of the L3MBTL1 constructs used for structural and functional study in this figure. For the L3MBTL1-H3.3 construct, a Gly-Gly-Gly linker was used to separate L3MBTL1 and the covalently attached histone 3.3[28–34] segment.
(B) Insertion of proline into a shallow cavity of symmetry-related L3MBTL1 pocket 1 in the Kme2-L3MBTL1 complex is shown. The Pro ring is sandwiched within the narrow walls at the base of the pocket. The interior parts of the surface are colored in gray, and exterior parts are colored by their electrostatic potential as described for Figure 1C. The Pro ligand is shown in the dotted van der Waals radius representation. The “EPS” peptide segment is shown, with part of the Ser omitted from the drawing for clarity.
(C) Relative positioning of PS step containing C-terminal L3MBTL1 segment in pocket 1 and Kme2 in pocket 2 on the same L3MBTL1 surface in the Kme2-L3MBTL1 complex.
(D) Stereo view of the PS step containing H3.3 SAPSTGG segment with its Pro ring inserted into pocket 1 of the Kme2-L3MBTL1-H3.3[28–34] complex. Key residues participating in pocket formation are shown in stick representation (cyan) with main-chain atoms omitted for clarity. Water molecules are shown as small red spheres and hydrogen bonds indicated by dashed red lines.
(E) Stereo view of the relative positioning of PS step containing H3.3 SAPSTGG segment in pocket 1 and Kme2 in pocket 2 on the same L3MBTL1 surface in the Kme2- L3MBTL1-H3.3[28–34] complex. Note that the type II β-turn formed at the “APST” motif in pocket 1 helps to direct the C-terminal GG segment of H3.3 toward the Kme2-bound pocket 2. Water molecules are shown as small red spheres and hydrogen bonds indicated by dashed red lines.

Figure 4.
Figure 4. Stereo Views of Pocket 2 Comparing Superpositioned Kme2-Bound Wild-Type and Mutant L3MBTL1 Complexes
(A–D) The wild-type L3MBTL1 complex with bound Kme2 is shown in beige (A–D). The D355N mutant complex is shown in light blue (A), the D355A mutant is shown in dark blue (B), the N358Q mutant is shown in light green (C), and the N358A mutant is shown in dark green (D). Kme2 was not detected in pocket 2 for complexes with D355N (A), D355A (B), N358Q (C), and N358A (D).
Superpositioning is based on least-squares fitting of Cα atoms within the second MBT module (349–416) of L3MBTL1.

The above figures are reprinted by permission from Cell Press: Mol Cell (2007, 28, 677-691) copyright 2007.

Figures were selected by an automated process.