De novo design of a transmembrane Zn 2+ -transporting four-helix bundle

• DOI: 10.1126/science.1261172
• Publication Date: 2014-12-19T08:12:06Z
• Authors: Nathan H. Joh; Tuo Wang; Manasi P. Bhate; Rudresh Acharya; Yibing Wu; Michael Grabe; Mei Hong; Gevorg Grigoryan; William F. DeGrado
• Keywords: Helix bundle; Cooperativity; Protein design; Helix (gastropod)

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