A large intrinsically disordered region in SKIP and its disorder-order transition induced by PPIL1 binding revealed by NMR

Xingsheng Wang, Shaojie Zhang, Jiahai Zhang, Xiaojuan Huang, Chao Xu, Weiwei Wang, Zhijun Liu, Jihui Wu, Yunyu Shi

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Intrinsically disordered proteins or protein regions play an important role in fundamental biological processes. During spliceosome activation, a large structural rearrangement occurs. The Prp19 complex and related factors are involved in the catalytic activation of the spliceosome. Recent mass spectrometric analyses have shown that Ski interaction protein (SKIP) and peptidylprolyl isomerase-like protein 1 (PPIL1) are Prp19-related factors that constitute the spliceosome B, B*, and C complexes. Here, we report that a highly flexible region of SKIP (SKIPN, residues 59-129) is intrinsically disordered. Upon binding to PPIL1, SKIPN undergoes a disorder-order transition. A highly conserved fragment of SKIP (residues 59-79) called the PPIL1-binding fragment (PBF) was sufficient to bind PPIL1. The structure of PBF·PPIL1 complex, solved by NMR, shows that PBF exhibits an ordered structure and interacts with PPIL1 through electrostatic and hydrophobic interactions. Three subfragments in the PBF (residues 59-67, 68-73, and 74-79) show hook-like backbone structure, and interactions between these subfragments are necessary for PBF·PPIL1 complex formation. PPIL1 is a cyclophilin family protein. It is recruited by SKIP into the spliceosome by a region other than the peptidylprolyl isomerase active site. This enables the active site of PPIL1 to remain open in the complex and still function as a peptidylprolyl cis/trans-isomerase or molecular chaperon to facilitate the folding of other proteins in the spliceosomes. The large disordered region in SKIP provides an interaction platform. Its disorder-order transition, induced by PPIL1 binding, may adapt the requirement for a large structural rearrangement occurred in the activation of spliceosome.

Original languageEnglish (US)
Pages (from-to)4951-4963
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number7
DOIs
StatePublished - Feb 12 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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