Folding of Aquaporin 1: multiple evidence that helix 3 can shift out of the membrane core

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Minttu T. Virkki, Nitin Agrawal, Elin Edsbäcker, Susana Cristobal, Arne Elofsson, Anni Kauko
Publisher: Wiley-Blackwell Publishing
Publication year: 2014
Journal: Protein Science
Volume number: 23
Issue number: 7
Start page: 981
End page: 992
eISSN: 1469-896X


Abstract

The folding of most integral membrane proteins follows a two-step process: initially, individual transmembrane helices are inserted into the membrane by the Sec translocon. Thereafter, these helices fold to shape the final conformation of the protein. However, for some proteins, including Aquaporin 1 (AQP1), the folding appears to follow a more complicated path. AQP1 has been reported to first insert as a four-helical intermediate, where helix 2 and 4 are not inserted into the membrane. In a second step, this intermediate is folded into a six-helical topology. During this process, the orientation of the third helix is inverted. Here, we propose a mechanism for how this reorientation could be initiated: first, helix 3 slides out from the membrane core resulting in that the preceding loop enters the membrane. The final conformation could then be formed as helix 2, 3, and 4 are inserted into the membrane and the reentrant regions come together. We find support for the first step in this process by showing that the loop preceding helix 3 can insert into the membrane. Further, hydrophobicity curves, experimentally measured insertion efficiencies and MD-simulations suggest that the barrier between these two hydrophobic regions is relatively low, supporting the idea that helix 3 can slide out of the membrane core, initiating the rearrangement process.


Keywords

Aquaporin 1

Last updated on 2019-19-10 at 04:31