The structure of active serpin 1K from Manduca sexta

Jinping Li, Zhulun Wang, Bertram Canagarajah, Haobo Jiang, Michael Kanost, Elizabeth J. Goldsmith

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Background: The reactive-center loops (RCL) of serpins undergo large conformational changes triggered by the interaction with their target protease. Available crystallographic data suggest that the serpin RCL is polymorphic, but the relevance of the observed conformations to the competent active structure and the conformational changes that occur on binding target protease has remained obscure. New high-resolution data on an active serpin, serpin 1K from the moth hornworm Manduca sexta, provide insights into how active serpins are stabilized and how conformational changes are induced by protease binding. Results: The 2.1 Å structure shows that the RCL of serpin 1K, like that of active α1-antitrypsin, is canonical, complimentary and ready to bind to the target protease between P3 and P3, (where P refers to standard protease nomenclature). In the hinge region (P17-P13), however, the RCL of serpin 1 K, like ovalbumin and α1-antichymotrypsin, forms tight interactions that stabilize the five-stranded closed form of β sheet A. These interactions are not present in, and are not compatible with, the observed structure of active α1-antitrypsin. Conclusions: Serpin 1 K may represent the best resting conformation for serpins - canonical near P1, but stabilized in the closed conformation of β sheet A. By comparison with other active serpins, especially α1-antitrypsin, a model is proposed in which interaction with the target protease near P1 leads to conformational changes in β sheet A of the serpin.

Original languageEnglish (US)
Pages (from-to)103-109
Number of pages7
JournalStructure
Volume7
Issue number1
DOIs
StatePublished - Jan 15 1999

Keywords

  • Active serpin structure
  • Crystal structure
  • Reactive center loop
  • Serpin 1K

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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