Identification of the prolyl isomerase domain of <i>Escherichia coli</i> trigger factor

Hesterkamp, Thomas; Bukau, Bernd

doi:10.1016/0014-5793(96)00351-1

Cited by 79 publications

(76 citation statements)

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“…One gene encoding trigger factor-like protein was found in the Arabidopsis genome and named as AtTIG. Trigger factors are distantly related to the FKBP family (Callebaut and Mornon, 1995;Hesterkamp and Bukau, 1996b).…”

Section: Resultsmentioning

confidence: 99%

“…Trigger factor is the major protein that cross-links to virtually all nascent chains of secretory and cytosolic proteins tested (Valent et al, 1995;Hesterkamp and Bukau, 1996a). Sequence analysis and substrate specificity suggests that trigger factor contains a central domain belonging to the FKBP family (Callebaut and Mornon, 1995;Hesterkamp and Bukau, 1996b). Besides the central PPIase domain, trigger factor has a ribosome binding domain at the N-terminal domain and its C-terminal domain may strengthen the binding (Hesterkamp et al, 1997).…”

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confidence: 99%

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Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

2004

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Immunophilins are defined as receptors for immunosuppressive drugs including cyclosporin A, FK506, and rapamycin. The cyclosporin A receptors are referred to as cyclophilins (CYPs) and FK506-and rapamycin-binding proteins are abbreviated as FKBPs. These two groups of proteins (collectively called immunophilins) share little sequence homology, but both have peptidyl prolyl cis/trans isomerase (PPIase) activity that is involved in protein folding processes. Studies have identified immunophilins in all organisms examined including bacteria, fungi, animals, and plants. Nevertheless, the physiological function of immunophilins is poorly understood in any organism. In this study, we have surveyed the genes encoding immunophilins in Arabidopsis genome. A total of 52 genes have been found to encode putative immunophilins, among which 23 are putative FKBPs and 29 are putative CYPs. This is by far the largest immunophilin family identified in any organism. Both FKBPs and CYPs can be classified into single domain and multiple domain members. The single domain members contain a basic catalytic domain and some of them have signal sequences for targeting to a specific organelle. The multiple domain members contain not only the catalytic domain but also defined modules that are involved in protein-protein interaction or other functions. A striking feature of immunophilins in Arabidopsis is that a large fraction of FKBPs and CYPs are localized in the chloroplast, a possible explanation for why plants have a larger immunophilin family than animals. Parvulins represent another family of PPIases that are unrelated to immunophilins in protein sequences and drug binding properties. Three parvulin genes were found in Arabidopsis genome. The expression of many immunophilin and parvulin genes is ubiquitous except for those encoding chloroplast members that are often detected only in the green tissues. The large number of genes and diversity of structure domains and cellular localization make PPIases a versatile superfamily of proteins that clearly function in many cellular processes in plants.Immunosuppressive drugs cyclosporin A (CsA), FK506, and rapamycin are used clinically in transplantation to prevent graft rejection. During the course to understand the molecular mechanisms of immunosuppression by CsA, FK506, and rapamycin, the cellular receptors of these drugs have been purified and characterized (Schreiber, 1991;Fruman et al., 1994). CsA binds to a family of receptors named cyclophilins (CyPs), and FK506 and rapamycin bind to a distinct set of receptors called FKBPs (FK506 and rapamycin-binding proteins). Cyclophilins and FKBPs are collectively referred to as immunophilins (Schreiber, 1991).The complexes formed by immunophilins and their cognate ligands are the functional modules for immunosuppression. The FKBP12-FK506 and CyPCsA complexes, but not their separate components, bind to and inhibit the activity of calcineurin, a Ca 21 , calmodulin-dependent protein phosphatase (Liu et al., 1991). Studies have demonstrated that inhib...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

2004

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“…Further biochemical studies on other known trigger factors, such as those of Cumpylobacter jejuni, Mycoplasmn genitalium and Haemophilus influenza, should indicate how much this protein family mimics the FKBP features [16]. According to Schreiber's 1241 definition of imunophilins, TigEC, due to its lack of affinity for FK506, was characterized as a member of a novel PPIase family [5].…”

Section: Discussionmentioning

confidence: 99%

An Internal FK506‐Binding Domain is the Catalytic Core of the Prolyl Isomerase Activity Associated with the Bacillus Subtilis Trigger Factor

Göthel

Schmid

Wipat

et al. 1997

European Journal of Biochemistry

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Two major families of peptidylprolyl cis-trans-isomerases, the cyclophilins and the structurally unrelated FK506-binding proteins (FKBPs), have been identified as cellular factors involved in protein folding in vitro. Here we report on the biochemical characterization of a second prolyl isomerase of Bacillus subtilis that was purified from a cyclophilin-negative (ppiB null) mutant and was shown to be the trigger factor (TigBS). N-terminal sequencing of 27 amino acid residues of the purified protein revealed 100% identity to the deduced sequence encoded by the tig gene, sequenced as a part of the B. subtilis genome project. The tigBS gene, located at 246" on the genetic map upstream of the cZpX and lonA,B genes, encodes an acidic protein (PI 4.3) of 47.5 kDa. Purified and recombinant TigBS-His proteins share the same substrate specificity and catalytic activity (kLdt/Km of 1.5 pM-' s-'); both are inhibited by the macrolide FK506 with IC,, the range of 500 nM. We also demonstrate that the prolyl isomerase activity of TigBS is mediated by an internal domain of about 13 kDa (homologous to FKPB12) that represents the catalytic core of the trigger factor.

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“…1B). The trigger factor (22)(23)(24)(25) and SlyD [product of the slyD (sensitive-to lysis) gene, a cytosolic Escherichia coli chaperone] (26)(27)(28)(29) belong to this family of folding enzymes. The chaperone domain of SlyD (the ''insertin-flap'' or IF domain) shows a unique fold (30) and is structurally not related to other chaperones.…”

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Chaperone domains convert prolyl isomerases into generic catalysts of protein folding

Jakob

Žoldák

Aumüller

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The cis/trans isomerization of peptide bonds before proline (prolyl bonds) is a rate-limiting step in many protein folding reactions, and it is used to switch between alternate functional states of folded proteins. Several prolyl isomerases of the FK506-binding protein family, such as trigger factor, SlyD, and FkpA, contain chaperone domains and are assumed to assist protein folding in vivo. The prolyl isomerase activity of FK506-binding proteins strongly depends on the nature of residue Xaa of the Xaa-Pro bond. We confirmed this in assays with a library of tetrapeptides in which position Xaa was occupied by all 20 aa. A high sequence specificity seems inconsistent with a generic function of prolyl isomerases in protein folding. Accordingly, we constructed a library of protein variants with all 20 aa at position Xaa before a rate-limiting cis proline and used it to investigate the performance of trigger factor and SlyD as catalysts of proline-limited folding. The efficiencies of both prolyl isomerases were higher than in the tetrapeptide assays, and, intriguingly, this high activity was almost independent of the nature of the residue before the proline. Apparently, the almost indiscriminate binding of the chaperone domain to the refolding protein chain overrides the inherently high sequence specificity of the prolyl isomerase site. The catalytic performance of these folding enzymes is thus determined by generic substrate recognition at the chaperone domain and efficient transfer to the active site in the prolyl isomerase domain.folding catalysis ͉ folding helpers ͉ folding mechanism ͉ SlyD ͉ trigger factor T he cis/trans isomerization of peptide bonds before proline (Xaa-Pro or prolyl bonds; Fig. 1A) is an intrinsically slow reaction that depends on the nature of the amino acid Xaa (1-3). It determines the rates of many protein folding reactions (4-6), is used as a molecular switch (7-16), and is catalyzed by prolyl isomerases (17-21). Most of the prolyl isomerases that assist in cellular protein folding contain catalytic domains that are homologous to human FKBP12 (FK-506 binding protein of 12 kDa; Fig. 1B) and chaperone domains, which interact transiently with non-native proteins (Fig. 1B). The trigger factor (22-25) and SlyD [product of the slyD (sensitive-to lysis) gene, a cytosolic Escherichia coli chaperone] (26-29) belong to this family of folding enzymes. The chaperone domain of SlyD (the ''insertin-flap'' or IF domain) shows a unique fold (30) and is structurally not related to other chaperones. The chaperone domain of trigger factor shows similarities with prefoldin (31)and SurA (32). FkpA (periplasmic FKBP of E. coli) (33-35) of prokaryotes and FKBP52 of eukaryotes (36) display similar combinations of prolyl isomerase and chaperone domains.FKBP-type prolyl isomerases are highly specific with regard to residue Xaa before the proline (37-39). An initial characterization of human FKBP12 with various proline-containing tetrapeptides and a protease-coupled assay (17) indicated that it catalyzes isomerizati...

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Identification of the prolyl isomerase domain of Escherichia coli trigger factor

Cited by 79 publications

References 14 publications

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis

An Internal FK506‐Binding Domain is the Catalytic Core of the Prolyl Isomerase Activity Associated with the Bacillus Subtilis Trigger Factor

Chaperone domains convert prolyl isomerases into generic catalysts of protein folding

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