TY - JOUR
T1 - Structural characterization of the multidomain regulatory protein Rv1364c from mycobacterium tuberculosis
AU - King-Scott, Jack
AU - Konarev, Petr V.
AU - Panjikar, Santosh
AU - Jordanova, Rositsa
AU - Svergun, Dmitri I.
AU - Tucker, Paul A.
PY - 2011/1/12
Y1 - 2011/1/12
N2 - The open reading frame rv1364c of Mycobacterium tuberculosis, which regulates the stress-dependent σ factor, σF, has been analyzed structurally and functionally. Rv1364c contains domains with sequence similarity to the RsbP/RsbW/RsbV regulatory system of the stress-response σ factor of Bacillus subtilis. Rv1364c contains, sequentially, a PAS domain (which shows sequence similarity to the PAS domain of the B. subtilis RsbP protein), an active phosphatase domain, a kinase (anti-σF like) domain and a C-terminal anti-σF antagonist like domain. The crystal structures of two PAS domain constructs (at 2.3 and 1.6 ) and a phosphatase/kinase dual domain construct (at 2.6 ) are described. The PAS domain is shown to bind palmitic acid but to have 100 times greater affinity for palmitoleic acid. The full-length protein can exist in solution as both monomer and dimer. We speculate that a switch between monomer and dimer, possibly resulting from fatty acid binding, affects the accessibility of the serine of the C-terminal, anti-σF antagonist domain for dephosphorylation by the phosphatase domain thus indirectly altering the availability of σF.
AB - The open reading frame rv1364c of Mycobacterium tuberculosis, which regulates the stress-dependent σ factor, σF, has been analyzed structurally and functionally. Rv1364c contains domains with sequence similarity to the RsbP/RsbW/RsbV regulatory system of the stress-response σ factor of Bacillus subtilis. Rv1364c contains, sequentially, a PAS domain (which shows sequence similarity to the PAS domain of the B. subtilis RsbP protein), an active phosphatase domain, a kinase (anti-σF like) domain and a C-terminal anti-σF antagonist like domain. The crystal structures of two PAS domain constructs (at 2.3 and 1.6 ) and a phosphatase/kinase dual domain construct (at 2.6 ) are described. The PAS domain is shown to bind palmitic acid but to have 100 times greater affinity for palmitoleic acid. The full-length protein can exist in solution as both monomer and dimer. We speculate that a switch between monomer and dimer, possibly resulting from fatty acid binding, affects the accessibility of the serine of the C-terminal, anti-σF antagonist domain for dephosphorylation by the phosphatase domain thus indirectly altering the availability of σF.
UR - http://www.scopus.com/inward/record.url?scp=78651257345&partnerID=8YFLogxK
U2 - 10.1016/j.str.2010.11.010
DO - 10.1016/j.str.2010.11.010
M3 - Article
C2 - 21220116
AN - SCOPUS:78651257345
SN - 0969-2126
VL - 19
SP - 56
EP - 69
JO - Structure
JF - Structure
IS - 1
ER -
