4WZF: Crystal Structural Basis For Rv0315, An Immunostimulatory Antigen And Pseudo Beta-1, 3-glucanase Of Mycobacterium Tuberculosis

Citation:
Abstract
Mycobacterium tuberculosis (Mtb) remains a leading cause of morbidity and mortality worldwide, as two billion people are latently infected with Mtb. To address Mtb drug resistance and the limitations of current vaccines, the characteristics of candidate Mtb vaccines need to be explored. Here, we report the three-dimensional structure of Rv0315 at 1.70 A resolution, a novel immunostimulatory antigen of Mtb, and demonstrate that Rv0315 is an inactive beta-1,3-glucanase of the glycoside hydrolase 16 (GH16) family. Our study further elaborates the molecular basis for the lack of glucan recognition by Rv0315. Rv0315 has a large open groove, and this particular topology cannot bind oligosaccharide chains in solution, thus explaining the lack of detectable hydrolytic activity towards its substrate. Additionally, we identified Glu-176, a conserved catalytic residue in GH16 endo-beta-1,3-glucanases, as essential for Rv0315 to induce immunological responses. These results indicate that Rv0315 likely diverged from a broad-specificity ancestral GH16 glucanase, and this inactive member of the GH16 family offers new insights into the GH16 glucanase. Together, our findings suggest that an inactive beta-1,3-glucanase in Mtb drives T-helper 1 (Th1) immune responses, which may help develop more effective vaccines against Mtb infection.
PDB ID: 4WZFDownload
MMDB ID: 134650
PDB Deposition Date: 2014/11/19
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4WZF: monomeric; determined by author
Molecular Components in 4WZF
Label Count Molecule
Protein (1 molecule)
1
1,3-beta-glucanase
Molecule annotation
Chemicals (3 molecules)
1
1
2
2
* Click molecule labels to explore molecular sequence information.

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