Folding of Aquaporin 1: multiple evidence that helix 3 can shift out of the membrane core
2014 (English)In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 23, no 7, 981-992 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 23, no 7, 981-992 p.
membrane protein; translocon recognition; protein folding; hydrophobicity; molecular dynamics
Basic Medicine Biological Sciences
IdentifiersURN: urn:nbn:se:liu:diva-109129DOI: 10.1002/pro.2483ISI: 000337669800014PubMedID: 24777974OAI: oai:DiVA.org:liu-109129DiVA: diva2:737529