2xa6 | pdb_00002xa6
STRUCTURAL BASIS FOR HOMODIMERIZATION OF THE SRC-ASSOCIATED DURING MITOSIS, 68 KD PROTEIN (SAM68) QUA1 DOMAIN
Structural highlights
Function[KHDR1_HUMAN] Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export.[1] [2] [3] [4] [UniProtKB:Q60749][UniProtKB:Q8UUW7] Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase.[5] [6] [7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSam68 (Src-associated during mitosis, 68 kDa) is a prototypical member of the STAR (signal transducer and activator of RNA) family of RNA-binding proteins. STAR proteins bind mRNA targets and modulate cellular processes such as cell cycle regulation and tissue development in response to extracellular signals. Sam68 has been shown to modulate alternative splicing of the pre-mRNAs of CD44 and Bcl-xL, which are linked to tumor progression and apoptosis. Sam68 and other STAR proteins recognize bipartite RNA sequences and are thought to function as homodimers. However, the structural and functional roles of the self-association are not known. Here, we present the solution structure of the Sam68 Qua1 homodimerization domain. Each monomer consists of two antiparallel alpha-helices connected by a short loop. The two subunits are arranged perpendicular to each other in an unusual four-helix topology. Mutational analysis of Sam68 in vitro and in a cell-based assay revealed that the Qua1 domain and residues within the dimerization interface are essential for alternative splicing of a CD44 minigene. Together, our results indicate that the Qua1 homodimerization domain is required for regulation of alternative splicing by Sam68. Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain.,Meyer NH, Tripsianes K, Vincendeau M, Madl T, Kateb F, Brack-Werner R, Sattler M J Biol Chem. 2010 Sep 10;285(37):28893-901. Epub 2010 Jul 6. PMID:20610388[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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