The structural basis for glycerol permeation by human AQP7

Zhang, Li; Yao, Deqiang; Xia, Ying; Zhou, Fu; Zhang, Qing; Wang, Qian; Qin, An; Zhao, Jie; Li, Dianfan; Li, Yan; Zhou, Lu; Cao, Yu

doi:10.1016/j.scib.2020.12.006

Cited by 12 publications

(11 citation statements)

References 44 publications

(39 reference statements)

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“…However, at pH 7.4, AQP10 did not allow glycerol permeation ( 37 ). This result was inconsistent with another study that observed that hAQP10 allows glycerol permeation at neutral pH using a scintillation counter to measure 14 C-glycerol uptake ( 38 ). Since cancer cells have an altered pH compared to normal cells, the changes in pH may also alter AQP function and should evaluated.…”

Section: Aquaporin Structure and Functioncontrasting

confidence: 84%

Aquaporins: New players in breast cancer progression and treatment response

et al. 2022

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Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other small molecules and ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including water homeostasis, fat metabolism, proliferation, migration, and adhesion. Previous structural and functional studies highlight a strong biological relationship between AQP protein expression, localization, and key biological functions in normal and cancer tissues, where aberrant AQP expression correlates with tumorigenesis and metastasis. In this review, we discuss the roles of AQP1, AQP3, AQP4, AQP5, and AQP7 in breast cancer progression and metastasis, including the role of AQPs in the tumor microenvironment, to highlight potential contributions of stromal-derived to epithelial-derived AQPs to breast cancer. Emerging evidence identifies AQPs as predictors of response to cancer therapy and as targets for increasing their sensitivity to treatment. However, these studies have not evaluated the requirements for protein structure on AQP function within the context of breast cancer. We also examine how AQPs contribute to a patient’s response to cancer treatment, existing AQP inhibitors and how AQPs could serve as novel predictive biomarkers of therapy response in breast cancer. Future studies also should evaluate AQP redundancy and compensation as mechanisms used to overcome aberrant AQP function. This review highlights the need for additional research into how AQPs contribute molecularly to therapeutic resistance and by altering the tumor microenvironment.

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Section: Aquaporin Structure and Functioncontrasting

confidence: 84%

Aquaporins: New players in breast cancer progression and treatment response

et al. 2022

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“…Although it is unexpected to find a C2 symmetry on the tetrameric ring of hDERL1s, a higher oligomer with lower symmetry is precedented in other studies. For example, glycerol aquaporin AQP10 and AQP7 were reported to form a homotetramer, but both have slightly different conformations among the protomers in the tetramer (23,24). hDERL1 tetramer is primarily maintained by the interactions between loops 5 and 1 from neighboring protomers, and very limited interactions were identified on the TM helices between protomers (Fig.…”

Section: The Tetrameric Hderl1 Ring With C2 Symmetrymentioning

confidence: 99%

The cryo-EM structure of an ERAD protein channel formed by tetrameric human Derlin-1

Rao

Yao

et al. 2021

Sci. Adv.

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Endoplasmic reticulum–associated degradation (ERAD) is a process directing misfolded proteins from the ER lumen and membrane to the degradation machinery in the cytosol. A key step in ERAD is the translocation of ER proteins to the cytosol. Derlins are essential for protein translocation in ERAD, but the mechanism remains unclear. Here, we solved the structure of human Derlin-1 by cryo–electron microscopy. The structure shows that Derlin-1 forms a homotetramer that encircles a large tunnel traversing the ER membrane. The tunnel has a diameter of about 12 to 15 angstroms, large enough to allow an α helix to pass through. The structure also shows a lateral gate within the membrane, providing access of transmembrane proteins to the tunnel, and thus, human Derlin-1 forms a protein channel for translocation of misfolded proteins. Our structure is different from the monomeric yeast Derlin structure previously reported, which forms a semichannel with another protein.

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“…Since hDHHC3 contains 16 cysteines, iodoacetamide was introduced to block the possible disulfide bond formation between cysteine residues during the purification. Iodoacetamide is a widely used cysteine modification compound in the membrane protein purification and crystallization [ 25 , 26 ]. The protein purification started with Strep-Tactin affinity chromatography, which was followed by size exclusion chromatography using a Superdex 200 Increase 10/300 column ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

Structural Exploration on Palmitoyltransferase DHHC3 from Homo sapiens

et al. 2022

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DHHC3 belongs to a family of DHHC palmitoyltransferase, which catalyzes the S-palmitoylation of target proteins by attaching a fatty acyl group to a cysteine. Recently, DHHC3 has been demonstrated to be a promising antitumor target in cancer therapeutics. However, the detailed structure and catalysis mechanism of DHHC3 remain elusive, considering its sequence diversity from the DHHC homologues with known crystal structures. Here, we described the expression and purification of human DHHC3 (hDHHC3) and truncated hDHHC3 with the flexible N-terminal domain (NTD) removed. Purified hDHHC3 proteins were used under various conditions for protein crystallization. LAMTOR1, one of the interacting proteins of hDHHC3 to facilitate the crystallization, was further identified by mass spectrometry and co-immunoprecipitation assay. The structural exploration using cryogenic electronic microscopy (cryo-EM) on the inactive hDHHS3 mutant showed a typical sideview of membrane proteins. These results provide a preliminary guidance for the structural determination of DHHC3.

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The structural basis for glycerol permeation by human AQP7

Cited by 12 publications

References 44 publications

Aquaporins: New players in breast cancer progression and treatment response

Aquaporins: New players in breast cancer progression and treatment response

The cryo-EM structure of an ERAD protein channel formed by tetrameric human Derlin-1

Structural Exploration on Palmitoyltransferase DHHC3 from Homo sapiens

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