3M9H

Crystal structure of the amino terminal coiled coil domain of the Mycobacterium tuberculosis proteasomal ATPase Mpa

Summary for 3M9H

• Entry DOI: 10.2210/pdb3m9h/pdb
• Related: 3M91 3M9B 3M9D
• Descriptor: Proteasome-associated ATPase (2 entities in total)
• Functional Keywords: four helix antiparallel bundle, atp-binding, chaperone, nucleotide-binding, proteasome, s-nitrosylation, virulence
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 6
• Total formula weight: 37488.49

Authors

Li, H.,Wang, T. (deposition date: 2010-03-22, release date: 2010-10-27, Last modification date: 2024-02-21)

Primary citation

Wang, T.,Darwin, K.H.,Li, H.
Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation.
Nat.Struct.Mol.Biol., 17:1352-1357, 2010

PubMed Abstract: Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an α-helix in Pup. Our work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.

PubMed: 20953180
DOI: 10.1038/nsmb.1918

Experimental method

X-RAY DIFFRACTION (2 Å)