Raver1中的一个肽基序通过与PTB RRM2结构域相互作用介导剪接抑制。
A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain.
作者信息
Rideau Alexis P, Gooding Clare, Simpson Peter J, Monie Tom P, Lorenz Mike, Hüttelmaier Stefan, Singer Robert H, Matthews Stephen, Curry Stephen, Smith Christopher W J
机构信息
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, UK.
出版信息
Nat Struct Mol Biol. 2006 Sep;13(9):839-48. doi: 10.1038/nsmb1137. Epub 2006 Aug 27.
Polypyrimidine tract-binding protein (PTB) is a regulatory splicing repressor. Raver1 acts as a PTB corepressor for splicing of alpha-tropomyosin (Tpm1) exon 3. Here we define a minimal region of Raver1 that acts as a repressor domain when recruited to RNA. A conserved [S/G][I/L]LGxxP motif is essential for splicing repressor activity and sufficient for interaction with PTB. An adjacent proline-rich region is also essential for repressor activity but not for PTB interaction. NMR analysis shows that LLGxxP peptides interact with a hydrophobic groove on the dorsal surface of the RRM2 domain of PTB, which constitutes part of the minimal repressor region of PTB. The requirement for the PTB-Raver1 interaction that we have characterized may serve to bring the additional repressor regions of both proteins into a configuration that allows them to synergistically effect exon skipping.
聚嘧啶序列结合蛋白（PTB）是一种调控性剪接抑制因子。Raver1作为PTB的共抑制因子，参与α-原肌球蛋白（Tpm1）外显子3的剪接。在此，我们确定了Raver1的一个最小区域，该区域在被招募到RNA时可作为抑制结构域。一个保守的[S/G][I/L]LGxxP基序对于剪接抑制活性至关重要，并且足以与PTB相互作用。相邻的富含脯氨酸区域对于抑制活性也必不可少，但对于与PTB的相互作用并非必需。核磁共振分析表明，LLGxxP肽与PTB的RRM2结构域背表面的疏水凹槽相互作用，该凹槽构成了PTB最小抑制区域的一部分。我们所描述的PTB与Raver1相互作用的要求，可能有助于使两种蛋白质的其他抑制区域形成一种构型，从而使它们能够协同作用导致外显子跳跃。
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