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PDBsum entry 2peh
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Protein binding
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PDB id
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2peh
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References listed in PDB file
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Key reference
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Title
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U2af-Homology motif interactions are required for alternative splicing regulation by spf45.
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Authors
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L.Corsini,
S.Bonnal,
S.Bonna,
J.Basquin,
M.Hothorn,
K.Scheffzek,
J.Valcárcel,
M.Sattler.
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Ref.
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Nat Struct Biol, 2007,
14,
620-629.
[DOI no: ]
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PubMed id
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Abstract
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The U2AF-homology motif (UHM) mediates protein-protein interactions between
factors involved in constitutive RNA splicing. Here we report that the splicing
factor SPF45 regulates alternative splicing of the apoptosis regulatory gene FAS
(also called CD95). The SPF45 UHM is necessary for this activity and binds
UHM-ligand motifs (ULMs) present in the 3' splice site-recognizing factors
U2AF65, SF1 and SF3b155. We describe a 2.1-A crystal structure of SPF45-UHM in
complex with a ULM peptide from SF3b155. Features distinct from those of
previously described UHM-ULM structures allowed the design of mutations in the
SPF45 UHM that selectively impair binding to individual ULMs. Splicing assays
using the ULM-selective SPF45 variants demonstrate that individual UHM-ULM
interactions are required for FAS splicing regulation by SPF45 in vivo. Our data
suggest that networks of UHM-ULM interactions are involved in regulating
alternative splicing.
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Figure 1.
(a) Domain alignment of proteins that contain a UHM. (b)
Alignment of ULM sequences in U2AF65, SF1 and SF3b155. Conserved
residues are colored as follows: blue, basic residues preceding
conserved tryptophan; yellow, conserved tryptophan; orange,
acidic and Asn/Gln-type residues following tryptophan; green,
conserved and potentially phosphorylated serine and threonine
residues; purple, proline adjacent to threonine. (c) Schematic
drawing of 3' splice sites in spliceosomal complexes E and A.
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Figure 4.
(a) Ribbon representation of SPF45-UHM with stick
representation of SF3b155-ULM5 peptide. (b) Details of the
molecular recognition of SPF45-UHM and SF3b155-ULM5.
Experimental omit-electron density map contoured at 1.8  (blue)
surrounds a stick representation of residues 337–342 of the
SF3b155 peptide (orange). SPF45-UHM residues involved in ULM
coordination are shown in gray. (c) Structures of the
U2AF65-UHM–SF1-ULM complex (left, PDB 1O0P) and the
U2AF35-UHM–U2AF65-ULM complex (right, PDB 1JMT).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
620-629)
copyright 2007.
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