Rasmus Kock Flygaard

Abstract Integrins are heterodimeric membrane proteins acting as mechanosensing receptors. Nine human α-subunits contain a ligand binding αI domain, but how ligands activate αI integrins are not understood. We present cryo-EM structures of the αI integrin αMβ2 in complex with the C3d ligand. The ligand-bound αI domain appears to have two major opposite orientations relative to the β2 subunit.

Abstract Active transport by Ca2+-ATPases of the P-type ATPase family maintain a very low cytosolic calcium concentration and steep electrochemical gradients. Detailed mechanisms of this transport have been described from structures of mammalian sarco/endoplasmic reticulum Ca2+-ATPases (SERCA) stabilized by inhibitors at specific intermediate steps of the transport cycle. An essentially irreversible step is crucial to prevent reflux in active transport against steep gradients.

We have concerns with a recent paper by Yu and colleagues, published in Science Advances on 28 October 2022 (1). The paper reports cryo–electron microscopy (cryo-EM) structures for human sodium-potassium-chloride cotransporter (hNKCC1) in both apo state and with loop diuretic inhibitor compounds bumetanide and furosemide.