2PEH

Crystal structure of the UHM domain of human SPF45 in complex with SF3b155-ULM5

Summary for 2PEH

• Entry DOI: 10.2210/pdb2peh/pdb
• Related: 2PE8
• Descriptor: Splicing factor 45, Splicing factor 3B subunit 1 (3 entities in total)
• Functional Keywords: rrm, uhm, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q96I25; Nucleus speckle: O75533
• Total number of polymer chains: 4
• Total formula weight: 25993.90

Authors

Corsini, L.,Basquin, J.,Hothorn, M.,Sattler, M. (deposition date: 2007-04-03, release date: 2007-06-26, Last modification date: 2024-11-13)

Primary citation

Corsini, L.,Bonna, S.,Basquin, J.,Hothorn, M.,Scheffzek, K.,Valcarcel, J.,Sattler, M.
U2AF-homology motif interactions are required for alternative splicing regulation by SPF45.
Nat.Struct.Mol.Biol., 14:620-629, 2007

PubMed Abstract: 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.

PubMed: 17589525
DOI: 10.1038/nsmb1260

Experimental method

X-RAY DIFFRACTION (2.11 Å)