Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Dispatched uses Na flux to power release of lipid-modified Hedgehog.
Journal, issue, pages	Nature, Vol. 599, Issue 7884, Page 320-324, Year 2021
Publish date	Oct 27, 2021
Authors	Qianqian Wang / Daniel E Asarnow / Ke Ding / Randall K Mann / Jason Hatakeyama / Yunxiao Zhang / Yong Ma / Yifan Cheng / Philip A Beachy /
PubMed Abstract	The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters and to H-driven transporters of the RND family, enables tissue-patterning activity of the lipid-modified ...The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters and to H-driven transporters of the RND family, enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly -localized sites of embryonic expression. Here we determine a cryo-electron microscopy structure of the mouse protein Dispatched homologue 1 (DISP1), revealing three Na ions coordinated within a channel that traverses its transmembrane domain. We find that the rate of Hedgehog export is dependent on the Na gradient across the plasma membrane. The transmembrane channel and Na binding are disrupted in DISP1-NNN, a variant with asparagine substitutions for three intramembrane aspartate residues that each coordinate and neutralize the charge of one of the three Na ions. DISP1-NNN and variants that disrupt single Na sites retain binding to, but are impaired in export of the lipid-modified Hedgehog protein to the SCUBE2 acceptor. Interaction of the amino-terminal signalling domain of the Sonic hedgehog protein (ShhN) with DISP1 occurs via an extensive buried surface area and contacts with an extended furin-cleaved DISP1 arm. Variability analysis reveals that ShhN binding is restricted to one extreme of a continuous series of DISP1 conformations. The bound and unbound DISP1 conformations display distinct Na-site occupancies, which suggests a mechanism by which transmembrane Na flux may power extraction of the lipid-linked Hedgehog signal from the membrane. Na-coordinating residues in DISP1 are conserved in PTCH1 and other metazoan RND family members, suggesting that Na flux powers their conformationally driven activities.
External links	Nature / PubMed:34707294 / PubMed Central
Methods	EM (single particle)
Resolution	2.5 - 3.2 Å
Structure data	24614 7rph EMDB-24614, PDB-7rph: Cryo-EM structure of murine Dispatched 'R' conformation Method: EM (single particle) / Resolution: 2.5 Å 24615 7rpi EMDB-24615, PDB-7rpi: Cryo-EM structure of murine Dispatched 'T' conformation Method: EM (single particle) / Resolution: 2.5 Å 24616 7rpj EMDB-24616, PDB-7rpj: Cryo-EM structure of murine Dispatched NNN mutant Method: EM (single particle) / Resolution: 3.2 Å 24617 7rpk EMDB-24617, PDB-7rpk: Cryo-EM structure of murine Dispatched in complex with Sonic hedgehog Method: EM (single particle) / Resolution: 2.7 Å
Chemicals	ChemComp-NA: Unknown entry ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-AV0: Lauryl Maltose Neopentyl Glycol ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-HOH: WATER ChemComp-6OE: (2S)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(hexanoyloxy)propyl hexanoate ChemComp-CA: Unknown entry ChemComp-ZN: Unknown entry ChemComp-SO4: SULFATE ION
Source	mus musculus (house mouse)
Keywords	MEMBRANE PROTEIN / RND transporter / Hedgehog binding / Sterol sensing domain / sodium binding