3m91

Crystal structure of the prokaryotic ubiquitin-like protein (Pup) complexed with the amino terminal coiled coil of the Mycobacterium tuberculosis proteasomal ATPase Mpa

spinqualitylabelsall models 3m91, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3m91 is a 4 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: mpa (MYCTU), pup (MYCTU) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PUP_MYCTU] Protein modifier that is covalently attached to lysine residues of substrate proteins, thereby targeting them for proteasomal degradation. The tagging system is termed pupylation. Among the identified substrates are the FabD, PanB and Mpa proteins. Publication Abstract from PubMed 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 alpha-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. Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation.,Wang T, Darwin KH, Li H Nat Struct Mol Biol. 2010 Oct 17. PMID:20953180 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATPase 3D structures

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