AlphaFold2: Transporting structural biology towards integrative approaches

Posted by daviskd2 on Thursday, October 13, 2022 in News.

Have you been itching to use AlphaFold to study your protein of interest? You can “model” your study after the work of Diego del Alamo, of the Mchaourab and Meiler labs, who recently published a study of an APC transporter using this technology.

Amino Acid-Polyamine-Organocation (APC) transporters are responsible for exchanging amino acids and ions across membranes. Mutations in eukaryotic APC transporters contribute to several diseases such as phenylketonuria and cancer. Diego’s publication, however, focuses on the APC transporter from Escherichia coli, GadC, which helps the organism survive extreme acid stress.

Combining AlphaFold2 and double electron-electron resonance (DEER) spectroscopy, the labs show that GadC is homogenous at neutral pH and isomerizes between inward- and outward-facing conformations at low pH. Furthermore, they highlighted several structural conformations that were dependent on pH but not on substrate.

The study underscores the power of combining computational and experimental approaches to tackle structural biology questions.

Read all about it here! ~ Steven D. Walker

The figure shows the proposed transport mechanism of GABA and glutamate by GadC. Isomerization from inward-facing to outward-facing is more likely at low pH, and with substrates bound. Substrates lower the free energy barrier to isomerize between these states. Figure adapted from del Alamo, et al.