Crystallographic study of universal stress protein Rv2623 from Mycobacterium tuberculosis H37Rv

Approximately one-third of the population is infected with Mycobacterium tuberculosis, but in over 90% of infections remains clinically latent (1). Unfortunately, the mechanism of the host-pathogen interaction is poorly understood, mainly the mechanisms employed by M. tuberculosis to survive in a nutritionally deprived and an anoxic environment during latency (2). The adaptation to such an extreme environment involves differential expression of genes that respond to iron limitation, alternative carbon metabolism and hypoxia (3). Consequently, anaerobic and nutritionally starved cultures can be used as models for study of the physiological state of M. tuberculosis during latency (4). Using these approaches, it has been discovered that oxygen-starved M. tuberculosis, M. bovis BCG and M. smegmatis express a novel class of proteins whose counterparts in other organisms comprise the universal stress protein (USP), or UspA, family (5, 6, 7). Universal stress protein Rv2623 has been found to be expressed under hypoxia in 2-D gel analysis of M. tuberculosis and M. bovis BCG (5, 6). Furthermore, since it has also been observed that Rv2623 is expressed following phagocytosis of M. tuberculosis (8), the universal stress proteins, particularly Rv2623, might play a role in the resistance of the bacterial cells against different stress factors encountered during infection of macrophages. We determined the structure of the first universal stress protein Rv2623 from M. tuberculosis containing two tandem Usp domains.