PDBsum entry 2rpp

Transcription

PDB id: 2rpp

Contents

Protein chain

89 a.a. *

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

2rpp

Name:

Transcription

Title:

Solution structure of tandem zinc finger domain 12 in muscleblind-like protein 2

Structure:

Muscleblind-like protein 2. Chain: a. Fragment: zinc finger domain, unp residues 7-82. Synonym: muscleblind-like protein-like, muscleblind-like protein-like 39, muscleblind-like protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mbnl2, mbll, mbll39, mlp1. Expressed in: cell-free synthesis.

NMR struc:

20 models

Authors:

C.Abe,W.Dang,K.Tsuda,Y.Muto,M.Inoue,T.Kigawa,T.Terada,M.Shirouzu, S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

F.He et al. (2009). Solution structure of the RNA binding domain in the human muscleblind-like protein 2. Protein Sci, 18, 80-91. PubMed id: 19177353 DOI: 10.1002/pro.17

Date:

24-Jun-08 Release date: 12-May-09

Protein chain

Q5VZF2  (MBNL2_HUMAN) -  Muscleblind-like protein 2 from Homo sapiens

Seq: 373 a.a.

Struc: 89 a.a.*

* PDB and UniProt seqs differ at 12 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1002/pro.17

Protein Sci 18:80-91 (2009)

PubMed id: 19177353

Solution structure of the RNA binding domain in the human muscleblind-like protein 2.

F.He, W.Dang, C.Abe, K.Tsuda, M.Inoue, S.Watanabe, N.Kobayashi, T.Kigawa, T.Matsuda, T.Yabuki, M.Aoki, E.Seki, T.Harada, Y.Tomabechi, T.Terada, M.Shirouzu, A.Tanaka, P.Güntert, Y.Muto, S.Yokoyama.

ABSTRACT

The muscleblind-like (MBNL) proteins 1, 2, and 3, which contain four CCCH zinc finger motifs (ZF1-4), are involved in the differentiation of muscle inclusion by controlling the splicing patterns of several pre-mRNAs. Especially, MBNL1 plays a crucial role in myotonic dystrophy. The CCCH zinc finger is a sequence motif found in many RNA binding proteins and is suggested to play an important role in the recognition of RNA molecules. Here, we solved the solution structures of both tandem zinc finger (TZF) motifs, TZF12 (comprising ZF1 and ZF2) and TZF34 (ZF3 and ZF4), in MBNL2 from Homo sapiens. In TZF12 of MBNL2, ZF1 and ZF2 adopt a similar fold, as reported previously for the CCCH-type zinc fingers in the TIS11d protein. The linker between ZF1 and ZF2 in MBNL2 forms an antiparallel beta-sheet with the N-terminal extension of ZF1. Furthermore, ZF1 and ZF2 in MBNL2 interact with each other through hydrophobic interactions. Consequently, TZF12 forms a single, compact global fold, where ZF1 and ZF2 are approximately symmetrical about the C2 axis. The structure of the second tandem zinc finger (TZF34) in MBNL2 is similar to that of TZF12. This novel three-dimensional structure of the TZF domains in MBNL2 provides a basis for functional studies of the CCCH-type zinc finger motifs in the MBNL protein family.

Selected figure(s)

Figure 2.
Solution structure of the TZF12 domain in human MBNL2. (A) Stereo-view of the best 20 structures of the TZF12 domain (residues Val8-Asn82). ZF1 and ZF2 of TZF12 are colored aquamarine and coral, respectively. (B) Ribbon presentation of the lowest energy structure of the TZF12 domain. The colors for the backbones of ZF1 and ZF2 are the same as in A. The side chains of the ligand residues and the zinc ions are shown in yellow and gray, respectively. The side chains of the hydrophobic residues that constitute the hydrophobic core of TZF12 are shown in green. The ribbon diagram in the right panel is rotated horizontally by 90[deg] from that on the left. (C) Ribbon diagrams of TZF12 with the side chains of the positively charged and aromatic residues of ZF1 (left panel) and ZF2 (right panel), which are shown in blue and magenta, respectively. (D) Electrostatic surface potential of the TZF12 domain. The blue and red colors represent positive and negative electrostatic surface potential, respectively. (E) Hydrophobic and positively charged surface residues of the TZF12 domain. In C, D, and E, the ZF1 and ZF2 surface orientations (left and right panel) were obtained by 45[deg] and [minus sign]45[deg] vertical rotations of the ribbon structure on the left in B. The ribbon diagrams (C), the electrostatic potential (D), and the hydrophobic surfaces (E) have the same orientation. The cyan and red ellipses on the surfaces (D, E) of TZF12 mark the pockets formed by the conserved residues. The red ellipse marks the pocket that results from the formation of a compact global fold with the tandem zinc fingers.

Figure 4.
Comparison of the CCCH-type zinc finger motif structures of TIS11d and MBNL2. (A) Superposition of the ribbon diagrams of the TZF12 and TZF34 domains of MBNL2 with the ligand residue side-chains and zinc ions. (B) Superposition of the ribbon diagrams of ZF1 and ZF2 of TIS11d and ZF1-4 of MBNL2 with the ligand residue side-chains and zinc ions. ZF1 and ZF2 of TIS11d are shown in green and blue, respectively. The colors of ZF1-ZF4 of MBNL2 are the same as in Figures 2 Figure 2-and and3.3 Figure 3-. (C) Expanded view of the pocket region with the side chains of the conserved residues. The colors of the side chains are the same as in D --F. (D --F) Ribbon presentations with the side chains of the conserved positively charged and aromatic residues for ZF1 of TIS11d (D), ZF1 of MBNL2 (E), and ZF2 of MBNL2 (F). (G --L) Surface representations showing hydrophobic and positively charged residues of the ZF1-RNA complex of TIS11d (G), ZF1 of MBNL2 (H), ZF2 of MBNL2 (I), the ZF2-RNA complex of TIS11d (J), ZF3 of MBNL2 (K), and ZF4 of MBNL2 (L). The RNA is shown in yellow in (G) and (J). Positively charged residues are colored blue, and aliphatic and aromatic hydrophobic residues are in green and magenta, respectively. The cyan and red ellipses mark pockets 1-2 and pocket 3, respectively. (M, N) Surface superposition of the ZF1 complexed with RNA in TIS11d with ZF1 (M) and ZF2 (N) of the TZF12 in MBNL2. The surfaces of the ZF1 of TIS11d, and of ZF1 and ZF2 of TZF12 in MBNL2 are colored green, light blue, and orange, respectively. The conserved residues of the ZF1 in TIS11d and the TZF12 in MBNL2 with the red annotations are colored blue and red, respectively. The RNA is depicted by yellow sticks. Figures M and N were generated by PyMOL program (DeLano Scientific LLC).

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2009, 18, 80-91) copyright 2009.

Figures were selected by an automated process.