| Structural highlights
Function
[ABC1_MYCTU] Involved in the translocation of an unknown substrate across the membrane. Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation. Required for virulence.[1] [2]
Publication Abstract from PubMed
The Mycobacterium tuberculosis ATP-binding cassette transporter Rv1747 is a putative exporter of cell wall biosynthesis intermediates. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting Forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). The structures of FHA-1 and FHA-2 were determined by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, respectively. Relative to the canonical 11-strand beta-sandwich FHA domain fold of FHA-1, FHA-2 is circularly permuted and lacking one beta-strand. Nevertheless, the two share a conserved pThr-binding cleft. FHA-2 is less stable and more dynamic than FHA-1, yet binds model pThr peptides with moderately higher affinity ( approximately 50 muM versus 500 muM equilibrium dissociation constants). Based on NMR relaxation and chemical shift perturbation measurements, when joined within a polypeptide chain, either FHA domain can bind either linker pThr to form intra- and intermolecular complexes. We hypothesize that this enables tunable phosphorylation-dependent multimerization to regulate Rv1747 transporter activity.
Biophysical Characterization of the Tandem FHA Domain Regulatory Module from the Mycobacteriumtuberculosis ABC Transporter Rv1747.,Heinkel F, Shen L, Richard-Greenblatt M, Okon M, Bui JM, Gee CL, Gay LM, Alber T, Av-Gay Y, Gsponer J, McIntosh LP Structure. 2018 May 17. pii: S0969-2126(18)30164-3. doi:, 10.1016/j.str.2018.04.018. PMID:29861345[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Molle V, Soulat D, Jault JM, Grangeasse C, Cozzone AJ, Prost JF. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol Lett. 2004 May 15;234(2):215-23. doi:, 10.1016/j.femsle.2004.03.033. PMID:15135525 doi:http://dx.doi.org/10.1016/j.femsle.2004.03.033
- ↑ Curry JM, Whalan R, Hunt DM, Gohil K, Strom M, Rickman L, Colston MJ, Smerdon SJ, Buxton RS. An ABC transporter containing a forkhead-associated domain interacts with a serine-threonine protein kinase and is required for growth of Mycobacterium tuberculosis in mice. Infect Immun. 2005 Aug;73(8):4471-7. doi: 10.1128/IAI.73.8.4471-4477.2005. PMID:16040957 doi:http://dx.doi.org/10.1128/IAI.73.8.4471-4477.2005
- ↑ Heinkel F, Shen L, Richard-Greenblatt M, Okon M, Bui JM, Gee CL, Gay LM, Alber T, Av-Gay Y, Gsponer J, McIntosh LP. Biophysical Characterization of the Tandem FHA Domain Regulatory Module from the Mycobacteriumtuberculosis ABC Transporter Rv1747. Structure. 2018 May 17. pii: S0969-2126(18)30164-3. doi:, 10.1016/j.str.2018.04.018. PMID:29861345 doi:http://dx.doi.org/10.1016/j.str.2018.04.018
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