Structural and functional insight into the universal stress protein family

Abstract

We present the crystal structures of two universal stress proteins (USP) from Archaeoglobus fulgidus and Nitrosomonas europaea in both apo-and ligand-bound forms. This work is the first complete synthesis of the structural properties of 26 USP available in the Protein Data Bank, over 75% of which were determined by structure genomics centers with no additional information provided. The results of bioinformatic analyses of all available USP structures and their sequence homologs revealed that these two new USP structures share overall structural similarity with structures of USPs previously determined. Clustering and cladogram analyses, however, show how they diverge from other members of the USP superfamily and show greater similarity to USPs from organisms inhabiting extreme environments. We compared them with other archaeal and bacterial USPs and discuss their similarities and differences in context of structure, sequential motifs, and potential function. We also attempted to group all analyzed USPs into families, so that assignment of the potential function to those with no experimental data available would be possible by extrapolation.

A Universal Stress Protein (USP) in Mycobacteria Binds cAMP

“…1D) (45). Surprisingly, neither MSMEG_3811 nor Rv1636 contain a canonical CNB domain, and instead they are annotated as members of the USP superfamily (46,47).…”

“…Crystal structures of several USP family members show that ATP binds between ␤1 and ␤4, in a pocket composed of residues from ␣1, ␤1, ␤2, and ␤4 (47). The triphosphate is bound by a loop featuring a conserved Walker A-like motif (see above) and often coordinated by additional magnesium or manganese ions (47,49). To understand the unique binding behavior of Rv1636/MSMEG_3811, i.e.…”

“…The dimer interface is formed mainly by the C terminus of each monomer through a conserved, strongly hydrophobic VL(J/ V)V motif in ␤5 (Fig. 1D) (47). In contrast to Rv1636 apo, the loop with the Walker A-like ATP-binding motif in MSMEG_3811 is closer to the nucleotide-binding pocket due to the parallel orientation of ␤4 and ␤5, whereas ␤5 of Rv1636 apo is swapped between monomers and inserted between ␤4-and ␤5 of the partner monomer (Fig.…”

Transcriptome-Based Analysis of the Pantoea stewartii Quorum-Sensing Regulon and Identification of EsaR Direct Targets

“…The gene uspA codes for the universal stress global response regulator and is divergently transcribed from uspB, encoding the predicted universal stress response protein B. Universal stress proteins (USPs) are overproduced in response to a variety of stresses and afford the organism a mechanism to survive under unsuitable conditions, though by unknown pathways (36). EsaR represses production of UspA and other stress response genes at low cell density, tamping down the apparent stress response of P. stewartii when it is present in the leaf tissue during early stages of infection.…”

Crystallization and preliminary X-ray diffraction analysis of UspE fromEscherichia coli

“…The expression of Usps in bacteria is triggered in response to a large variety of adverse environmental factors such as heat and the presence of uncouplers, polymyxin, cycloserine, oxidants, metals, ethanol, nutrient starvation or DNA-damaging agents (Siegele, 2005;Tkaczuk et al, 2013). The overproduced Usps have been shown to play an important role in stress resistance and to aid survival through various mechanisms in several bacterial species (Nyströ m & Neidhardt, 1994).…”