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PDBsum entry 1wdy
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis for recognition of 2',5'-Linked oligoadenylates by human ribonuclease l.
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Authors
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N.Tanaka,
M.Nakanishi,
Y.Kusakabe,
Y.Goto,
Y.Kitade,
K.T.Nakamura.
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Ref.
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EMBO J, 2004,
23,
3929-3938.
[DOI no: ]
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PubMed id
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Abstract
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An interferon-induced endoribonuclease, ribonuclease L (RNase L), is implicated
in both the molecular mechanism of action of interferon and the fundamental
control of RNA stability in mammalian cells. RNase L is catalytically active
only after binding to an unusual activator molecule containing a
5'-phosphorylated 2',5'-linked oligoadenylate (2-5A), in the N-terminal half.
Here, we report the crystal structure of the N-terminal ankyrin repeat domain
(ANK) of human RNase L complexed with the activator 2-5A. This is the first
structural view of an ankyrin repeat structure directly interacting with a
nucleic acid, rather than with a protein. The ANK domain folds into eight
ankyrin repeat elements and forms an extended curved structure with a concave
surface. The 2-5A molecule is accommodated at a concave site and directly
interacts with ankyrin repeats 2-4. Interestingly, two structurally equivalent
2-5A binding motifs are found at repeats 2 and 4. The structural basis for 2-5A
recognition by ANK is essential for designing stable 2-5As with a high
likelihood of activating RNase L.
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Figure 1.
Figure 1 Crystal structure of ANK complexed with 2-5A. (A)
Structural and functional domains of RNase L. Ankyrin repeats
are shown starting with blue at repeat 1 and ending with red at
repeat 8. (B) Structure of the predominant trimeric species of
2-5A ((pp)p(A2'p5')[2]A) (Kerr and Brown, 1978). (C, D) Surface
(top) and ribbon (bottom) representations of the ANK/2-5A
complex. Ankyrin repeats (R1 -R8) are shown as in (A). The bound
2-5A molecule is shown as a ball-and-stick model. The view in
(D) was obtained by rotating the view in (C) by 90°.
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Figure 3.
Figure 3 Recognition of 2-5A by ANK. (A) Stereodiagram showing
the mode of 2-5A binding to ANK. The carbon atoms of ANK are
colored as in Figure 1, and those of the bound 2-5A molecule are
shown in white. Possible hydrogen bonds or salt bridges are
indicated by dashed lines, and distances (in Å) are given. The
refined model is superimposed on the weighted 2|F[o]| -|F[c]|
map (1.5  ,
yellow) and the |F[o]| -|F[c]| omit map of 2-5A (4.5 ,
orange), calculated at 1.8 Å resolution. Bound water molecules
are shown as spheres (cyan). (B, C) Recognition of the first and
third AMP moieties of 2-5A by repeats 4 and 2, respectively, of
ANK.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2004,
23,
3929-3938)
copyright 2004.
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