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PDBsum entry 3sxl
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RNA binding domain
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PDB id
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3sxl
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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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Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of sex-Lethal.
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Authors
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S.M.Crowder,
R.Kanaar,
D.C.Rio,
T.Alber.
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Ref.
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Proc Natl Acad Sci U S A, 1999,
96,
4892-4897.
[DOI no: ]
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PubMed id
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Abstract
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By binding specific RNA transcripts, the Sex-lethal protein (SXL) governs sexual
differentiation and dosage compensation in Drosophila melanogaster. To
investigate the basis for RNA binding specificity, we determined the crystal
structure of the tandem RNA recognition motifs (RRMs) of SXL. Both RRMs adopt
the canonical RRM fold, and the 10-residue, interdomain linker shows significant
disorder. In contrast to the previously determined structure of the two-RRM
fragment of heterogeneous nuclear ribonucleoprotein Al, SXL displays no
interdomain contacts between RRMs. These results suggest that the SXL RRMs are
flexibly tethered in solution, and RNA binding restricts the orientation of
RRMs. Therefore, the observed specificity for single-stranded, U-rich sequences
does not arise from a predefined, rigid architecture of the isolated SXL RRMs.
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Figure 1.
Fig. 1. Structure of the SXL RRM domains. (A)
Sigma-A-weighted, 2F[o]  F[c]
electron density map contoured at 1  illustrates
the quality of the map. Residues shown are Tyr-164-Phe-173. (B)
Ribbon diagram of SXL RRM1+2. Residues left out of the model for
lack of interpretable electron density include 111-123, 204-205
(interdomain linker), 276-282 (  2-  4 loop of
RRM2), and 290-294 (C terminus). RNP-1 and RNP-2 sequences are
colored in magenta. (C) Electrostatic surface potential of
SXLl+2 calculated with GRASP (blue = +5 kT > white = 0 kT > red
= 5 kT). The
absence of interdomain contacts in the SXL RRMl+2 crystal
structure is evident. Based on the structures of the RNA
complexes of UlA and U2B''/U2A', the most positive regions are
likely RNA binding surfaces.
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Figure 2.
Fig. 2. Relationship of RRM domains in SXL and hnRNP Al.
(A) Ribbon diagrams of Sex-lethal (green) and hnRNP A1 (red)
superimposed by using the secondary structural elements of RRM1
of each protein. In contrast to hnRNP A1 RRM2, RRM2 of SXL makes
no contacts with RRM1 and differs in orientation from RRM2 of
hnRNP A1 by a 92.5° rotation. (B) NMR chemical shift changes
for SXL RRM1+2 upon binding the sequence r(GU[8]C) (35). (Left)
SXL RRM1+2. (Right) RRM1+2 modeled with the RRM domains arranged
as in an hnRNP Al. Chemical shift changes are colored as
follows: blue (0-200 Hz), green (201-400 Hz), yellow (401-600
Hz), orange (601-800 Hz), and red (801-1000 Hz). Changes caused
by RNA binding are concentrated along the interdomain linker and
RNA binding surfaces.
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