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The N terminus of the serpin, tengpin, functions to trap the metastable native state
Author(s) -
Zhang Qingwei,
Buckle Ashley M,
Law Ruby H P,
Pearce Mary C,
Cabrita Lisa D,
Lloyd Gordon J,
Irving James A,
Smith A Ian,
Ruzyla Katya,
Rossjohn Jamie,
Bottomley Stephen P,
Whisstock James C
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400986
Subject(s) - trap (plumbing) , serpin , metastability , state (computer science) , chemistry , biology , physics , biochemistry , computer science , organic chemistry , algorithm , meteorology , gene
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—tengpinΔ51—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 tengpinΔ51. Therefore, the function of the N terminus in tengpin resembles protein cofactors that prevent mammalian serpins from spontaneously adopting the latent conformation.