The N terminus of the serpin, tengpin, functions to trap the metastable native state

Qingwei Zhang, Ashley Maurice Buckle, Ruby Hong Ping Law, Mary Catherine Pearce, Lisa Cabrita, Gordon Lloyd, James Alexander Irving, Alexander Ian Smith, Katya Ruzyla, Jamie Rossjohn, Stephen Paul Bottomley, James Whisstock

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

Serpins fold to a metastable native state and are susceptible to undergoing spontaneous conformational change to more stable conformers, such as the latent form. We investigated conformational change in tengpin, an unusual prokaryotic serpin from the extremophile Thermoanaerobacter tengcongensis. In addition to the serpin domain, tengpin contains a functionally uncharacterized 56-amino-acid amino-terminal region. Deletion of this domain creates a variant-tengpinDelta51-which folds past the native state and readily adopts the latent conformation. Analysis of crystal structures together with mutagenesis studies show that the N terminus of tengpin protects a hydrophobic patch in the serpin domain and functions to trap tengpin in its native metastable state. A 13-amino-acid peptide derived from the N terminus is able to mimick the role of the N terminus in stabilizing the native state of tengpinDelta51. Therefore, the function of the N terminus in tengpin resembles protein cofactors that prevent mammalian serpins from spontaneously adopting the latent conformation.
Original languageEnglish
Pages (from-to)658 - 663
Number of pages6
JournalEMBO Reports
Volume8
Issue number7
Publication statusPublished - 2007

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