%0 Journal Article %1 https://doi.org/10.1002/smll.202202056 %A Gössweiner-Mohr, Nikolaus %A Siligan, Christine %A Pluhackova, Kristyna %A Umlandt, Linnea %A Koefler, Sabina %A Trajkovska, Natasha %A Horner, Andreas %D 2022 %J Small %K EXC2075 PN3 PN3-11 curated %N 31 %P 2202056 %R https://doi.org/10.1002/smll.202202056 %T The Hidden Intricacies of Aquaporins: Remarkable Details in a Common Structural Scaffold %U https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202202056 %V 18 %X Abstract Evolution turned aquaporins (AQPs) into the most efficient facilitators of passive water flow through cell membranes at no expense of solute discrimination. In spite of a plethora of solved AQP structures, many structural details remain hidden. Here, by combining extensive sequence- and structural-based analysis of a unique set of 20 non-redundant high-resolution structures and molecular dynamics simulations of four representatives, key aspects of AQP stability, gating, selectivity, pore geometry, and oligomerization, with a potential impact on channel functionality, are identified. The general view of AQPs possessing a continuous open water pore is challenged and it is depicted that AQPs’ selectivity is not exclusively shaped by pore-lining residues but also by the relative arrangement of transmembrane helices. Moreover, this analysis reveals that hydrophobic interactions constitute the main determinant of protein thermal stability. Finally, a numbering scheme of the conserved AQP scaffold is established, facilitating direct comparison of, for example, disease-causing mutations and prediction of potential structural consequences. Additionally, the results pave the way for the design of optimized AQP water channels to be utilized in biotechnological applications.

@article{https://doi.org/10.1002/smll.202202056, abstract = {Abstract Evolution turned aquaporins (AQPs) into the most efficient facilitators of passive water flow through cell membranes at no expense of solute discrimination. In spite of a plethora of solved AQP structures, many structural details remain hidden. Here, by combining extensive sequence- and structural-based analysis of a unique set of 20 non-redundant high-resolution structures and molecular dynamics simulations of four representatives, key aspects of AQP stability, gating, selectivity, pore geometry, and oligomerization, with a potential impact on channel functionality, are identified. The general view of AQPs possessing a continuous open water pore is challenged and it is depicted that AQPs’ selectivity is not exclusively shaped by pore-lining residues but also by the relative arrangement of transmembrane helices. Moreover, this analysis reveals that hydrophobic interactions constitute the main determinant of protein thermal stability. Finally, a numbering scheme of the conserved AQP scaffold is established, facilitating direct comparison of, for example, disease-causing mutations and prediction of potential structural consequences. Additionally, the results pave the way for the design of optimized AQP water channels to be utilized in biotechnological applications.}, added-at = {2022-11-23T20:49:12.000+0100}, author = {Gössweiner-Mohr, Nikolaus and Siligan, Christine and Pluhackova, Kristyna and Umlandt, Linnea and Koefler, Sabina and Trajkovska, Natasha and Horner, Andreas}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/204782e4a5b543c181a29ff0b8066bec5/simtech}, doi = {https://doi.org/10.1002/smll.202202056}, eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.202202056}, interhash = {a5066fa69245849b8d16b193902ad4a6}, intrahash = {04782e4a5b543c181a29ff0b8066bec5}, journal = {Small}, keywords = {EXC2075 PN3 PN3-11 curated}, number = 31, pages = 2202056, timestamp = {2023-12-06T08:55:18.000+0100}, title = {The Hidden Intricacies of Aquaporins: Remarkable Details in a Common Structural Scaffold}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202202056}, volume = 18, year = 2022 }