Molecular architecture of the human Prp19/CDC5L complex

Michael Grote, Elmar Wolf, Cindy L. Will, Ira Lemm, Dmitry E. Agafonov, Adrian Schomburg, Wolfgang Fischle, Henning Urlaub, Reinhard Lührmann

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


Protein complexes containing Prp19 play a central role during catalytic activation of the spliceosome, and Prp19 and its related proteins are major components of the spliceosome's catalytic core RNP. To learn more about the spatial organization of the human Prp19 (hPrp19)/CDC5L complex, which is comprised of hPrp19, CDC5L, PRL1, AD002, SPF27, CTNNBL1, and HSP73, we purified native hPrp19/CDC5L complexes from HeLa cells stably expressing FLAG-tagged AD002 or SPF27. Stoichiometric analyses indicated that, like Saccharomyces cerevisiae NTC (nineteen complex), the human Prp19/CDC5L complex contains four copies of hPrp19. Salt treatment identified a stable core comprised of CDC5L, hPrp19, PRL1, and SPF27. Proteinprotein interaction studies revealed that SPF27 directly interacts with each component of the hPrp19/CDC5L complex core and also elucidated several additional, previously unknown interactions between hPrp19/CDC5L complex components. Limited proteolysis of the hPrp19/CDC5L complex revealed a protease-resistant complex comprised of SPF27, the C terminus of CDC5L, and the N termini of PRL1 and hPrp19. Under the electron microscope, purified hPrp19/CDC5L complexes exhibit an elongated, asymmetric shape with a maximum dimension of ∼20 nm. Our findings not only elucidate the molecular organization of the hPrp19/CDC5L complex but also provide insights into potential protein-protein interactions at the core of the catalytically active spliceosome.

Original languageEnglish (US)
Pages (from-to)2105-2119
Number of pages15
JournalMolecular and cellular biology
Issue number9
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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