Integrin alpha IIb beta 3 in a membrane environment remains the same height after Mn2+ activation when observed by cryoelectron tomography.
Integrins perform the critical function of signalling cell attachment to the extracellular matrix or to other cells. This signalling is done through a structural change propagated bidirectionally across the plasma membrane. Integrin activation has been extensively studied with ectodomain constructs, but the structural change within intact, membrane-bound molecules remains a subject of live debate. Using cryoelectron tomography, we examined the simplest predication of the different integrin activation models, i.e., the change in height of the molecules. Analysis using techniques that compensate for the missing wedge during alignment and averaging and that search for patterns in the structure of the aligned molecular subvolumes extracted from the tomogram reveals that the vast majority of molecules show no dramatic height change upon Mn(2+)-induced activation of membrane-bound integrins when compared with an inactive integrin control group. Thus, the result is inconsistent with the switchblade activation model.
Ye
Feng
F
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4380, USA.
Liu
Jun
J
Winkler
Hanspeter
H
Taylor
Kenneth A
KA
D002462:Cell Membrane / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008345:Manganese / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D011487:Protein Conformation; D014054:Tomography / Q000379:methods*
D008081:Liposomes; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D008345:Manganese