Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7

Maré, Sofia W. de; Venskutonytė, Raminta; Eltschkner, Sandra; Groot, Bert L. de; Lindkvist‐Petersson, Karin

doi:10.1016/j.str.2019.11.011

Cited by 48 publications

(47 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our structure, the interaction area of the NAA/NPS motif is ∼10% smaller than the interaction area of the conserved NPA/NPA motif of GlpF. Our data on the interaction area are also in agreement with those for the NAA/NPS motif in the 1.9 Å 6QZI structure (de Maré et al, 2019).…”

Section: Structural Analysissupporting

confidence: 87%

“…A comparison of the MD analyses of de Maré et al (2019) and those in the present paper reveals several similarities:…”

Section: Summary/analysissupporting

confidence: 54%

“…A comparison of the de Maré et al (2019) 1.9 Å 6QZI structure or the 2.2 Å 6QZJ structure (both of which were deposited to the PDB on March 11, 2019) vs. our 6N1G structure reveals that the two higher-resolution structures and ours are in general agreement for most of the protein. However, we note several important differences:…”

Section: Discussionmentioning

confidence: 55%

“…The protein expressed by de Maré et al (2019) to obtain their 6QZI and 6QZJ structures had its N- and C-termini truncated. AQP7 lacking its termini is not physiologically appropriate because it fails to traffic appropriately to the plasma membrane (unpublished).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF

et al. 2020

View full text Add to dashboard Cite

Xenopus oocytes expressing human aquaporin-7 (AQP7) exhibit greater osmotic water permeability and 3 H-glycerol uptake vs. those expressing the bacterial glycerol facilitator GlpF. AQP7-expressing oocytes exposed to increasing extracellular [glycerol] under isosmolal conditions exhibit increasing swelling rates, whereas GlpF-expressing oocytes do not swell at all. To provide a structural basis for these observed physiological differences, we performed X-ray crystallographic structure determination of AQP7 and molecular-dynamics simulations on AQP7 and GlpF. The structure reveals AQP7 tetramers containing two monomers with 3 glycerols, and two monomers with 2 glycerols in the pore. In contrast to GlpF, no glycerol is bound at the AQP7 selectivity filter (SF), comprising residues F74, G222, Y223, and R229. The AQP7 SF is resolved in its closed state because F74 blocks the passage of small solutes. Molecular dynamics simulations demonstrate that F74 undergoes large and rapid conformational changes, allowing glycerol molecules to permeate without orientational restriction. The more rigid GlpF imposes orientational constraints on glycerol molecules passing through the SF. Moreover, GlpF-W48 (analogous to AQP7-F74) undergoes rare but long-lasting conformational changes that block the pore to H 2 O and glycerol.

show abstract

Section: Structural Analysissupporting

confidence: 87%

“…A comparison of the MD analyses of de Maré et al (2019) and those in the present paper reveals several similarities:…”

Section: Summary/analysissupporting

confidence: 54%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, due to its colligative properties, organisms as diverse as algae, fungi, insects, and fishes can accumulate glycerol to alleviate osmotic stress or as an antifreeze metabolite [ 3 , 4 , 5 , 6 , 7 , 8 ]. Though glycerol may passively diffuse across cell membranes [ 9 ], its transport is greatly facilitated by a group of integral membrane proteins termed the aquaglyceroporins (Glps) [ 10 , 11 , 12 , 13 , 14 , 15 ]. Glps were first identified in bacteria as the Escherichia coli glycerol facilitator (GlpF), and they have been phylogenetically and functionally shown to belong to a superfamily of transmembrane water-conducting channels, the aquaporins [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Unravelling the Complex Duplication History of Deuterostome Glycerol Transporters

Yilmaz

Chauvigné

Ferré

et al. 2020

Cells

View full text Add to dashboard Cite

Transmembrane glycerol transport is an ancient biophysical property that evolved in selected subfamilies of water channel (aquaporin) proteins. Here, we conducted broad level genome (>550) and transcriptome (>300) analyses to unravel the duplication history of the glycerol-transporting channels (glps) in Deuterostomia. We found that tandem duplication (TD) was the major mechanism of gene expansion in echinoderms and hemichordates, which, together with whole genome duplications (WGD) in the chordate lineage, continued to shape the genomic repertoires in craniates. Molecular phylogenies indicated that aqp3-like and aqp13-like channels were the probable stem subfamilies in craniates, with WGD generating aqp9 and aqp10 in gnathostomes but aqp7 arising through TD in Osteichthyes. We uncovered separate examples of gene translocations, gene conversion, and concerted evolution in humans, teleosts, and starfishes, with DNA transposons the likely drivers of gene rearrangements in paleotetraploid salmonids. Currently, gene copy numbers and BLAST are poor predictors of orthologous relationships due to asymmetric glp gene evolution in the different lineages. Such asymmetries can impact estimations of divergence times by millions of years. Experimental investigations of the salmonid channels demonstrated that approximately half of the 20 ancestral paralogs are functional, with neofunctionalization occurring at the transcriptional level rather than the protein transport properties. The combined findings resolve the origins and diversification of glps over >800 million years old and thus form the novel basis for proposing a pandeuterostome glp gene nomenclature.

show abstract

Just passing through: Deploying aquaporins in microbial cell factories

Jenkins Sánchez,

Sips,

Van Bogaert

2024

Biotechnology Progress

View full text Add to dashboard Cite

As microbial membranes are naturally impermeable to even the smallest biomolecules, transporter proteins are physiologically essential for normal cell functioning. This makes transporters a key target area for engineering enhanced cell factories. As part of the wider cellular transportome, aquaporins (AQPs) are responsible for transporting small polar solutes, encompassing many compounds which are of great interest for industrial biotechnology, including cell feedstocks, numerous commercially relevant polyols and even weak organic acids. In this review, examples of cell factory engineering by targeting AQPs are presented. These AQP modifications aid in redirecting carbon fluxes and boosting bioconversions either by enhanced feedstock uptake, improved intermediate retention, increasing product export into the media or superior cell viability against stressors with applications in both bacterial and yeast production platforms. Additionally, the future potential for AQP deployment and targeting is discussed, showcasing hurdles and considerations of this strategy as well as recent advances and future directions in the field. By leveraging the natural diversity of AQPs and breakthroughs in channel protein engineering, these transporters are poised to be promising tools capable of enhancing a wide variety of biotechnological processes.

show abstract

Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7

Cited by 48 publications

References 49 publications

Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF

Aquaporin-7: A Dynamic Aquaglyceroporin With Greater Water and Glycerol Permeability Than Its Bacterial Homolog GlpF

Unravelling the Complex Duplication History of Deuterostome Glycerol Transporters

Just passing through: Deploying aquaporins in microbial cell factories

Contact Info

Product

Resources

About