4P6L

Crystal Structure of the Computationally Designed Transmembrane Metallotransporter in Octyl Glucoside

Summary for 4P6L

• Entry DOI: 10.2210/pdb4p6l/pdb
• Related: 4P6J 4P6K
• Descriptor: Computationally Designed Transporter of Zn(II) and proton (1 entity in total)
• Functional Keywords: transmembrane, transporter, de-novo designed, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 5906.87

Authors

Joh, N.H.,Acharya, R.,DeGrado, W.F. (deposition date: 2014-03-25, release date: 2014-12-24, Last modification date: 2024-10-30)

Primary citation

Joh, N.H.,Wang, T.,Bhate, M.P.,Acharya, R.,Wu, Y.,Grabe, M.,Hong, M.,Grigoryan, G.,DeGrado, W.F.
De novo design of a transmembrane Zn2+-transporting four-helix bundle.
Science, 346:1520-1524, 2014

PubMed Abstract: The design of functional membrane proteins from first principles represents a grand challenge in chemistry and structural biology. Here, we report the design of a membrane-spanning, four-helical bundle that transports first-row transition metal ions Zn(2+) and Co(2+), but not Ca(2+), across membranes. The conduction path was designed to contain two di-metal binding sites that bind with negative cooperativity. X-ray crystallography and solid-state and solution nuclear magnetic resonance indicate that the overall helical bundle is formed from two tightly interacting pairs of helices, which form individual domains that interact weakly along a more dynamic interface. Vesicle flux experiments show that as Zn(2+) ions diffuse down their concentration gradients, protons are antiported. These experiments illustrate the feasibility of designing membrane proteins with predefined structural and dynamic properties.

PubMed: 25525248
DOI: 10.1126/science.1261172

Experimental method

X-RAY DIFFRACTION (2.803 Å)