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PDBsum entry 1up1
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Nuclear protein
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PDB id
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1up1
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References listed in PDB file
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Key reference
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Title
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Crystal structure of human up1, The domain of hnrnp a1 that contains two RNA-Recognition motifs.
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Authors
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R.M.Xu,
L.Jokhan,
X.Cheng,
A.Mayeda,
A.R.Krainer.
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Ref.
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Structure, 1997,
5,
559-570.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is one of the
most abundant core proteins of hnRNP complexes in metazoan nuclei. It behaves as
a global regulator of alternative pre-mRNA splicing by antagonizing the
activities of several serine/arginine-rich splicing factors (SR proteins),
resulting in the activation of distal alternative 5' splice sites and skipping
of optional exons. Purified hnRNP A1 has nucleic acid annealing activity. The
protein also shuttles continuously between the nucleus and the cytoplasm, a
process mediated by signals within its C-terminal glycine-rich domain. The
N-terminal region of human hnRNP A1, termed unwinding protein 1 (UP1), contains
two RNA-recognition motifs (RRMs), RRM1 and RRM2. Understanding the structural
elements by which hnRNP A1 interacts with RNA will have broad implications for
studies of RNA processing. RESULTS: The crystal structure of UP1 has been
determined to 1.9 A resolution. Each RRM independently adopts the characteristic
RRM fold, consisting of a four-stranded antiparallel beta-pleated sheet and two
alpha helices packed on one side of the beta sheet. The two RRMs are
antiparallel and held in close contact, mainly by two Arg-Asp ion pairs. As a
result, the two four-stranded beta sheets are brought together to form an
extended RNA-binding surface. A segment of the linker connecting the two RRMs is
flexible in the absence of bound RNA, but the general location of the linker
suggests that it can make direct contacts with RNA. Comparison with other RRM
structures indicates that a short 310 helix, found immediately N-terminal to the
first beta strand in RRM1, may interact with RNA directly. CONCLUSIONS: The RRM
is one of the most common and best characterized RNA-binding motifs. In certain
cases, one RRM is sufficient for sequence-specific and high affinity RNA
binding; but in other cases, synergy between several RRMs within a single
protein is required. This study shows how two RRMs are organized in a single
polypeptide. The two independently folded RRMs in UP1 are held together in a
fixed geometry, enabling the two RRMs to function as a single entity in binding
RNA, and so explaining the synergy between the RRMs. The UP1 structure also
suggests that residues which lie outside of the RRMs can make potentially
important interactions with RNA.
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Figure 1.
Figure 1. Overall folding of UP1. (a) Ribbon diagram of the
UP1 structure, viewed from the front (b-sheet side) of the
molecule. The conserved RNP-2 and RNP-1 submotifs are colored
cyan and purple, respectively. Red indicates the disordered
portion of the linker region; its placement is not based on
electron density, but was included for clarity. The N terminus
starts at Pro7, and the C terminus ends at Ser182. (b) Side view
of the overall folding of UP1. Diagrams were generated with the
Ribbons program [67].
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
559-570)
copyright 1997.
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