PDBsum entry 2vh4

Hydrolase inhibitor

PDB id: 2vh4

Contents

Protein chains

380 a.a. *

Waters ×240

* Residue conservation analysis

PDB id:

2vh4

Name:

Hydrolase inhibitor

Title:

Structure of a loop c-sheet serpin polymer

Structure:

Tengpin. Chain: a, b. Fragment: serpin, residues 43-423. Synonym: serine protease inhibitor. Engineered: yes

Source:

Thermoanaerobacter tengcongensis. Organism_taxid: 273068. Strain: mb4. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.45Å R-factor: 0.196 R-free: 0.262

Authors:

Q.Zhang,R.H.P.Law,S.P.Bottomley,J.C.Whisstock,A.M.Buckle

Key ref:

Q.Zhang et al. (2008). A structural basis for loop C-sheet polymerization in serpins. J Mol Biol, 376, 1348-1359. PubMed id: 18234218 DOI: 10.1016/j.jmb.2007.12.050

Date:

19-Nov-07 Release date: 08-Jan-08

Protein chains

Q8R9P5  (Q8R9P5_CALS4) -  Serine protease inhibitor from Caldanaerobacter subterraneus subsp. tengcongensis (strain DSM 15242 / JCM 11007 / NBRC 100824 / MB4)

Seq: 423 a.a.

Struc: 380 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.jmb.2007.12.050

J Mol Biol 376:1348-1359 (2008)

PubMed id: 18234218

A structural basis for loop C-sheet polymerization in serpins.

Q.Zhang, R.H.Law, S.P.Bottomley, J.C.Whisstock, A.M.Buckle.

ABSTRACT

In this study, we report the X-ray crystal structure of an N-terminally truncated variant of the bacterial serpin, tengpin (tengpinDelta42). Our data reveal that tengpinDelta42 adopts a variation of the latent conformation in which the reactive center loop is hyperinserted into the A beta-sheet and removed from the vicinity of the C-sheet. This conformational change leaves the C beta-sheet completely exposed and permits antiparallel edge-strand interactions between the exposed portion of the reactive center loop of one molecule and strand s2C of the C beta-sheet of the neighboring molecule in the crystal lattice. Our structural data thus reveal that tengpinDelta42 forms a loop C-sheet polymer in the crystal lattice. In vivo serpins have a propensity to misfold and form long-chain polymers, a process that underlies serpinopathies such as emphysema, thrombosis and dementia. Native serpins are thought to polymerize via a loop A-sheet mechanism. However, studies on plasminogen activator inhibitor 1 and the S49P variant of human neuroserpin reveal that the latent form of these molecules can also polymerize. Polymerization of latent neuroserpin may be important for the development of familial encephalopathy with neuroserpin inclusion bodies. Our structural data provide a possible mechanism for polymerization by latent serpins.

Selected figure(s)

Figure 1.
Fig. 1. Schematic representation of the conformational states of serpins. The A β-sheet is in red, the C β-sheet is in yellow, the RCL is in magenta and the protease is in cyan.

Figure 6.
Fig. 6. Nondenaturing 12% (wt/vol) PAGE. TP-L: latent tengpinΔ42 polymer (dissolved crystals used for structural analysis); TP-N: native tengpinΔ31 polymer (after prior heating at 80 °C).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 376, 1348-1359) copyright 2008.

Figures were selected by an automated process.