6cah

NMR-based structure of the FHA-2 domain from Mycobacterium tuberculosis ABC transporter Rv1747

spinqualitylabelsall models 6cah Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cah is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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