9thz | pdb_00009thz
Crystal structure of HtpG chaperone in complex with AMPPNP
Structural highlights
FunctionHTPG_MYCTA Molecular chaperone. Has ATPase activity. Publication Abstract from PubMedHtpG(Mtb) 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(Mtb) 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(Mtb), in complex with the non-hydrolysable form of ATP. The crystal structure reveals that the HtpG(Mtb) 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(Mtb) directly interacts with Toll Like Receptor 4 with a nanomolar affinity, and that this interaction allows HtpG(Mtb) dimer to engage two host receptor molecules. This finding suggests that activation of Toll Like Receptor 4 by HtpG(Mtb) is due to its ability to induce the dimerisation of the host receptor, an essential step for initiating the entire signaling cascade. Structural and binding studies of the mycobacterial heat shock protein reveal a silent state and offer insights into dendritic cell activation.,Barra G, Sala M, Scala MC, Campiglia P, Kim HJ, Ruggiero A, Berisio R Int J Biol Macromol. 2026 Apr;353:151218. doi: 10.1016/j.ijbiomac.2026.151218. , Epub 2026 Mar 5. PMID:41794242[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
