title: The N terminus of the serpin, tengpin, functions to trap the metastable native state.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Buckle
authors.forename: Ruby H P
authors.initials: RH
authors.lastname: Law
authors.forename: Mary C
authors.initials: MC
authors.lastname: Pearce
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Cabrita
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lloyd
authors.forename: James A
authors.initials: JA
authors.lastname: Irving
authors.forename: A Ian
authors.initials: AI
authors.lastname: Smith
authors.forename: Katya
authors.initials: K
authors.lastname: Ruzyla
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Bottomley
authors.forename: James C
authors.initials: JC
authors.lastname: Whisstock
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D017124:Conserved Sequence; D003460:Crystallization; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D015843:Serpins / Q000737:chemistry* / Q000235:genetics; D013059:Spectrum Analysis, Raman; D046968:Thermoanaerobacter / Q000737:chemistry
chemical_list: D010455:Peptides; D015843:Serpins