6qv2 | pdb_00006qv2

Structure of ATPgS-bound outward-facing TM287/288 in complex with nanobody Nb_TM#2

spinqualitylabelsall models 6qv2, resolution 4.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qv2 is a 6 chain structure with sequence from Thermotoga maritima MSB8 and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 4.23Å Ligands: AGS, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed ABC exporters harness the energy of ATP to pump substrates across membranes. Extracellular gate opening and closure are key steps of the transport cycle, but the underlying mechanism is poorly understood. Here, we generated a synthetic single domain antibody (sybody) that recognizes the heterodimeric ABC exporter TM287/288 exclusively in the presence of ATP, which was essential to solve a 3.2 A crystal structure of the outward-facing transporter. The sybody binds to an extracellular wing and strongly inhibits ATPase activity by shifting the transporter's conformational equilibrium towards the outward-facing state, as shown by double electron-electron resonance (DEER). Mutations that facilitate extracellular gate opening result in a comparable equilibrium shift and strongly reduce ATPase activity and drug transport. Using the sybody as conformational probe, we demonstrate that efficient extracellular gate closure is required to dissociate the NBD dimer after ATP hydrolysis to reset the transporter back to its inward-facing state. The extracellular gate shapes the energy profile of an ABC exporter.,Hutter CAJ, Timachi MH, Hurlimann LM, Zimmermann I, Egloff P, Goddeke H, Kucher S, Stefanic S, Karttunen M, Schafer LV, Bordignon E, Seeger MA Nat Commun. 2019 May 21;10(1):2260. doi: 10.1038/s41467-019-09892-6. PMID:31113958 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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