PDBsum entry 1rgo

RNA binding protein

PDB id: 1rgo

Contents

Protein chain

70 a.a. *

DNA/RNA

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

1rgo

Name:

RNA binding protein

Title:

Structural basis for recognition of the mRNA class ii au-rich element by the tandem zinc finger domain of tis11d

Structure:

RNA (5'-r( Up Up Ap Up Up Up Ap Up U)-3'). Chain: d. Engineered: yes. Butyrate response factor 2. Chain: a. Synonym: tis11d protein, egf-response factor 2, erf-2. Engineered: yes

Source:

Synthetic: yes. Other_details: synthetic. Homo sapiens. Human. Organism_taxid: 9606. Gene: zfp36l2, brf2, tis11d, erf2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

B.P.Hudson,M.A.Martinez-Yamout,H.J.Dyson,P.E.Wright

Key ref:

B.P.Hudson et al. (2004). Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat Struct Mol Biol, 11, 257-264. PubMed id: 14981510 DOI: 10.1038/nsmb738

Date:

12-Nov-03 Release date: 02-Mar-04

Protein chain

P47974  (TISD_HUMAN) -  mRNA decay activator protein ZFP36L2 from Homo sapiens

Seq: 494 a.a.

Struc: 70 a.a.

DNA/RNA chain

U-U-A-U-U-U-A-U-U 9 bases

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb738

Nat Struct Mol Biol 11:257-264 (2004)

PubMed id: 14981510

Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d.

B.P.Hudson, M.A.Martinez-Yamout, H.J.Dyson, P.E.Wright.

ABSTRACT

The tandem zinc finger (TZF) domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation. The NMR structure of the TIS11d TZF domain bound to the RNA sequence 5'-UUAUUUAUU-3' comprises a pair of novel CCCH fingers of type CX(8)CX(5)CX(3)H separated by an 18-residue linker. The two TIS11d zinc fingers bind in a symmetrical fashion to adjacent 5'-UAUU-3' subsites on the single-stranded RNA via a combination of electrostatic and hydrogen-bonding interactions, with intercalative stacking between conserved aromatic side chains and the RNA bases. Sequence specificity in RNA recognition is achieved by a network of intermolecular hydrogen bonds, mostly between TIS11d main-chain functional groups and the Watson-Crick edges of the bases. The TIS11d structure provides insights into the RNA-binding functions of this large family of CCCH zinc finger proteins.

Selected figure(s)

Figure 3.
Figure 3. Solution structure of the RNA complex of TIS11d. (a) Stereo view of the best 20 structures superposed on backbone heavy atoms in ordered regions of the protein and RNA. The protein backbone is blue, the RNA backbone red, and RNA bases yellow. For clarity, only ordered regions of TIS11d (residues 153 -217) and RNA bases U2 -U9 are shown. (b) Ribbon representation of a single structure, in the same orientation as in a, showing the location and coordination of zinc in each of the fingers. Colors are the same as in a, with the addition of green side chains for the zinc-coordinating ligands. (c) Backbone superposition of the structure ensembles of fingers 1 and 2. Finger 1 (Arg153 -Phe180) is dark blue (backbone), green (zinc-coordinating side chains) and red (intercalating aromatic rings); the bound RNA (U6, A7, U8, U9) is orange. The corresponding colors for finger 2 are light blue, yellow, pink and yellow. Figures were generated using MolMol50.

Figure 4.
Figure 4. Molecular recognition of RNA by TIS11d and hydrogen bonding between TIS11d and RNA. (a) Molecular contact surface of a representative TIS11d TZF structure generated in GRASP51 showing surface topology. Green denotes convex surfaces. The locations of the (R/K)YKTEL motifs that form the U6 and U2 binding pockets are indicated. (b) Stereo view showing hydrogen-bonding interactions between finger 1 and the 3' UAUU subsite. The protein backbone is light blue, the RNA backbone and bases pale yellow, and the intercalating aromatic side chains green. Each of the intermolecular hydrogen bonds is designated with a number and identified by a red line and colored atoms (red, oxygen; white, hydrogen; blue, nitrogen). (c) Schematic figure summarizing hydrogen-bonding interactions (dotted lines) with each of the bases in both subsites of the ARE. The hydrogen bond numbers for finger 1 in part b are shown. Panels a and b were generated using MolMol50.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 257-264) copyright 2004.

Figures were selected by an automated process.