Name
Title | ||
|---|---|---|
Modeling Escherichia coli signal peptidase complex with bound substrate: determinants in the mature peptide influencing signal peptide cleavage |
Abstract | ||
|---|---|---|
BACKGROUND: Type I signal peptidases (SPases) are essential membrane-bound serine proteases responsible for the cleavage of signal peptides from proteins that are translocated across biological membranes. The crystal structure of SPase in complex with signal peptide has not been solved and their substrate-binding site and binding specificities remain poorly understood. We report here a structure-based model for Escherichia coli DsbA 13–25 in complex with its endogenous type I SPase. RESULTS: The bound structure of DsbA 13–25 in complex with its endogenous type I SPase reported here reveals the existence of an extended conformation of the precursor protein with a pronounced backbone twist between positions P3 and P1'. Residues 13–25 of DsbA occupy, and thereby define 13 subsites, S7 to S6', within the SPase substrate-binding site. The newly defined subsites, S1' to S6' play critical roles in the substrate specificities of E. coli SPase. Our results are in accord with available experimental data. CONCLUSION: Collectively, the results of this study provide interesting new insights into the binding conformation of signal peptides and the substrate-binding site of E. coli SPase. This is the first report on the modeling of a precursor protein into the entire SPase binding site. Together with the conserved precursor protein binding conformation, the existing and newly identified substrate binding sites readily explain SPase cleavage fidelity, consistent with existing biochemical results and solution structures of inhibitors in complex with E. coli SPase. Our data suggests that both signal and mature moiety sequences play important roles and should be considered in the development of predictive tools. |
Year | DOI | Venue |
|---|---|---|
2008 | 10.1186/1471-2105-9-S1-S15 | BMC Bioinformatics |
Keywords | Field | DocType |
Signal Peptide, Lipopeptide, Binding Groove, Signal Peptidase, Binding Conformation | Signal peptidase,Signal peptidase complex,Biology,Proteases,DsbA,Biochemistry,Peptide,Signal peptide,Bioinformatics,Protein structure,Peptide sequence | Journal |
Volume | Issue | ISSN |
9 | S-1 | 1471-2105 |
Citations | PageRank | References |
30 | 0.69 | 3 |
Authors | ||
3 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Khar Heng Choo | 1 | 129 | 3.79 |
| Joo Chuan Tong | 2 | 182 | 9.00 |
| Shoba Ranganathan | 3 | 689 | 36.60 |