The role of water coordination in the pH-dependent gating of hAQP10

Truelsen, Sigurd Friis; Missel, Julie Winkel; Gotfryd, Kamil; Pedersen, Per Amstrup; Gourdon, Pontus; Lindorff‐Larsen, Kresten; Hélix-Nielsen, Claus

doi:10.1016/j.bbamem.2021.183809

Cited by 4 publications

(2 citation statements)

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“…Intriguingly, a recent in silico study suggested the role of water coordination around His h1.‐3 and interactions with the conserved Glu 1.‐6 in H1 in the gating behavior of Hs AQP10. [ 158 ] Similarly, we found major differences in the interaction with Glu 1.‐6 , as outlined above and in the average number of H‐bonds the His forms with pore water molecules (Figure S20, Supporting Information). His95 h1.‐3 of Hs AQP4 forms at neutral pH on average 0.7 ± 0.5 H‐bonds with other pore lining amino acids, with 0.3 ± 0.3 H‐bonds to Glu 1.‐6 in H1 as calculated from the data presented in Figure S23, Supporting Information—the errors denote SEM, n = 4 chains.…”

Section: Resultssupporting

confidence: 57%

The Hidden Intricacies of Aquaporins: Remarkable Details in a Common Structural Scaffold

Goessweiner‐Mohr

Siligan

Pluháčková

et al. 2022

Small

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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.

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Section: Resultssupporting

confidence: 57%

The Hidden Intricacies of Aquaporins: Remarkable Details in a Common Structural Scaffold

Goessweiner‐Mohr

Siligan

Pluháčková

et al. 2022

Small

View full text Add to dashboard Cite

show abstract

“…However, interactions with Ser h1.-6 in L2 are not obvious from the high-resolution structures. Intriguingly, a recent in silico study suggested the role of water coordination around His h1.-3 and interactions with the conserved Glu 1.-6 in H1 in the gating behavior of Hs AQP10 (155). Similarly, we found major differences in the interaction with Glu 1.-6 , as outlined above and in the average number of H-bonds the His forms with pore water molecules ( Figure S20 ).…”

Section: Resultsmentioning

confidence: 99%

The hidden intricacies of aquaporins: Remarkable details in a common structural scaffold

Goessweiner‐Mohr

Siligan

Pluháčková

et al. 2022

Preprint

View full text Add to dashboard Cite

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 4 representatives, we identify key aspects of AQP stability, gating, selectivity, pore geometry and oligomerization, with a potential impact on channel functionality. We challenge the general view of AQPs possessing a continuous open water pore and depict that AQPs selectivity is not exclusively shaped by pore lining residues but also by the relative arrangement of transmembrane helices. Moreover, our analysis reveals that hydrophobic interactions constitute the main determinant of protein thermal stability. Finally, we establish a novel numbering scheme of the conserved AQP scaffold facilitating direct comparison and prediction of potential structural effects of e.g. disease-causing mutations. Additionally, our results pave the way for the design of optimized AQP water channels to be utilized in biotechnological applications.

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