An inverting basket model for AE1 transport.
We describe an "inverting basket" model for transport in the erythrocyte anion exchanger, AE1. The inverting basket is formed by the side chains of three putative key residues, two positively (Lys 826 and Arg 730) and one negatively (Glu 681) charged residue. We have tentatively chosen seven transmembrane helices, TM1, TM2, TM4, TM8, TM10, TM12 and TM13 to form a conical channel using the well-established Glu 681 of TM8 and candidates Lys 826 and Arg 730 of TM12-13 and TM10, respectively, to form the inverting basket. We assume that these residues bind to an anion and shift from outward facing (C(o)) to inward facing (C(i)) conformation without significant backbone movements to transport an anion across the membrane. The transition of the complex (residues and ion) from outward facing (C(o)) to inward facing (C(i)) constitutes one "basket" inversion. The barrier to inversion is composed of two major components: that of the anhydrous complex, which we refer to as a steric energy barrier and a dehydration effect due to the removal of charges in the complex from water in the channel. The steric barrier is dependent on the side chain charge and configuration and on the ion charge and size. The dehydration effect, for our model, ameliorates the steric barrier, in the case of the empty complex but less so for the monovalent and divalent ions. We conclude, that it is possible for a seven-helix bundle to have a steric barrier to basket inversion, but that hydration effects in thin hydrophobic barrier models may be more complex than usually envisioned.
Ramakrishnan
Vivek
V
Zoology Department and Center for Neuroscience, Brigham Young University, Provo, UT 84602, USA.
Busath
David D
DD
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D001692:Biological Transport; D003198:Computer Simulation; D004912:Erythrocytes / Q000378:metabolism*; D008954:Models, Biological
D001457:Anion Exchange Protein 1, Erythrocyte