Dimerization of ER-resident molecular chaperones mediated by ERp29

Nakao, Hitomi; Seko, Akira; Ito, Yukishige; Sakono, Masafumi

doi:10.1016/j.bbrc.2020.12.023

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…The amino acids in this motif point toward the same face of the CNX TMD, and our data show that the position of the motif within the membrane is important for client binding. It should be noted that CNX can also form (ERp29‐mediated) dimers (Nakao et al , 2021), which may affect intramembrane client binding and CNX may, for example, in fact be a dimer when it recognizes TMDs. Our data can also not rule out that further factors are involved in CNX client binding, as CNX has a large repertoire of interacting proteins in the ER that among others involve the membrane protein chaperone EMC (Christianson et al , 2011).…”

Section: Discussionmentioning

confidence: 99%

Intramembrane client recognition potentiates the chaperone functions of calnexin

et al. 2022

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One-third of the human proteome is comprised of membrane proteins, which are particularly vulnerable to misfolding and often require folding assistance by molecular chaperones. Calnexin (CNX), which engages client proteins via its sugar-binding lectin domain, is one of the most abundant ER chaperones, and plays an important role in membrane protein biogenesis. Based on mass spectrometric analyses, we here show that calnexin interacts with a large number of nonglycosylated membrane proteins, indicative of additional nonlectin binding modes. We find that calnexin preferentially bind misfolded membrane proteins and that it uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by calnexin, and identify sequence motifs within the calnexin TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of calnexin. Together, these data reveal a widespread role of calnexin client recognition in the lipid bilayer, which synergizes with its established lectin-based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome.

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Section: Discussionmentioning

confidence: 99%

Intramembrane client recognition potentiates the chaperone functions of calnexin

et al. 2022

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“…The amino acids in this motif point towards the same face of the CNX TMD, and our data show that the position of the motif within the membrane is important for client binding. It should be noted that CNX can also form ERp29-mediated dimers (Nakao et al , 2021), which may affect intra-membrane client binding. Our data cannot completely rule out that further factors are involved in CNX client binding, as CNX has a large repertoire of interacting proteins in the ER that e.g.…”

Section: Discussionmentioning

confidence: 99%

Intra-membrane client recognition potentiates the chaperone functions of Calnexin

Bloemeke

Meighen-Berger

Hitzenberger

et al. 2022

Preprint

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One third of the human proteome are membrane proteins. They are particularly vulnerable to misfolding, often requiring assistance by molecular chaperones. Calnexin (CNX), one of the most abundant ER chaperones, plays an important role in membrane protein biogenesis and engages clients via its sugar-binding lectin domain.Using mass spectrometric analyses, we show that Calnexin (CNX) interacts with a large number of non-glycosylated membrane proteins, suggesting additional binding modes. We find that misfolded membrane proteins are preferentially bound by CNX and that CNX uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by CNX and identify sequence motifs within the CNX TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of CNX.Together, this study reveals a widespread role of CNX client recognition in the lipid bilayer, which synergizes with its established lectin-based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome.

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The Development of Silk Glands and Transcriptome Aberration Induced by Cyantraniliprole in Bombyx Mori

Liu,

Qi,

et al. 2024

Preprint

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Dimerization of ER-resident molecular chaperones mediated by ERp29

Cited by 3 publications

References 29 publications

Intramembrane client recognition potentiates the chaperone functions of calnexin

Intramembrane client recognition potentiates the chaperone functions of calnexin

Intra-membrane client recognition potentiates the chaperone functions of Calnexin

The Development of Silk Glands and Transcriptome Aberration Induced by Cyantraniliprole in Bombyx Mori

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