Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered protein.
Pup (prokaryotic ubiquitin-like protein) from Mycobacterium tuberculosis is the first ubiquitin-like protein identified in non-eukaryotic cells. Although different ubiquitin-like proteins from eukaryotes share low sequence similarity, their 3D (three-dimensional) structures exhibit highly conserved typical ubiquitin-like folds. Interestingly, our studies reveal that Pup not only shares low sequence similarity, but also presents a totally distinguished structure compared with other ubiquitin-like superfamily proteins. Diverse structure predictions combined with CD and NMR spectroscopic studies all demonstrate that Pup is an intrinsically disordered protein. Moreover, 1H-15N NOE (nuclear Overhauser effect) data and CSI (chemical shift index) analyses indicate that there is a residual secondary structure at the C-terminus of Pup. In M. tuberculosis, Mpa (mycobacterium proteasomal ATPase) is the regulatory cap ATPase of the proteasome that interacts with Pup and brings the substrates to the proteasome for degradation. In the present paper, SPR (surface plasmon resonance) and NMR perturbation studies imply that the C-terminus of Pup, ranging from residues 30 to 59, binds to Mpa probably through a hydrophobic interface. In addition, phylogenetic analysis clearly shows that the Pup family belongs to a unique and divergent evolutionary branch, suggesting that it is the most ancient and deeply branched family among ubiquitin-like proteins. This might explain the structural distinction between Pup and other ubiquitin-like superfamily proteins.
Liao
Shanhui
S
Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
Shang
Qiang
Q
Zhang
Xuecheng
X
Zhang
Jiahai
J
Xu
Chao
C
Tu
Xiaoming
X
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D014452:Ubiquitins / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; C533288:Pup protein, Mycobacterium tuberculosis; D014452:Ubiquitins