9THZ
Crystal structure of HtpG chaperone in complex with AMPPNP
Summary for 9THZ
| Entry DOI | 10.2210/pdb9thz/pdb |
| Descriptor | Chaperone protein HtpG, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION (3 entities in total) |
| Functional Keywords | heat shock protein, tuberculosis, antigen, chaperone |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 2 |
| Total formula weight | 150189.98 |
| Authors | |
| Primary citation | Barra, G.,Sala, M.,Scala, M.C.,Campiglia, P.,Kim, H.J.,Ruggiero, A.,Berisio, R. Structural and binding studies of the mycobacterial heat shock protein reveal a silent state and offer insights into dendritic cell activation. Int.J.Biol.Macromol., 353:151218-151218, 2026 Cited by PubMed Abstract: HtpG of Mycobacterium tuberculosis is an ATP-dependent heat shock protein that assists the correct folding of nascent and stress-accumulated misfolded proteins, in concert with other chaperones. Besides playing a role in stress response, it is able to elicit an immune response against M. tuberculosis infection by activating Dendritic Cells in a Toll Like Receptor 4-mediated manner. However, we lack a full understanding of the molecular determinants of HtpG catalytic activity and Toll Like Receptor 4 activation, due to the lack of structural and biophysical data. Here, we report the first crystal structure of HtpG, in complex with the non-hydrolysable form of ATP. The crystal structure reveals that the HtpG dimer adopts a conformationally silent structure, that precludes the dimerisation of the chaperone catalytic domains needed for ATP hydrolysis. Also, binding studies show that HtpG directly interacts with Toll Like Receptor 4 with a nanomolar affinity, and that this interaction allows HtpG dimer to engage two host receptor molecules. This finding suggests that activation of Toll Like Receptor 4 by HtpG is due to its ability to induce the dimerisation of the host receptor, an essential step for initiating the entire signaling cascade. PubMed: 41794242DOI: 10.1016/j.ijbiomac.2026.151218 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.322 Å) |
Structure validation
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