Structural insights into the membrane chaperones for multi-pass membrane protein biogenesis

Bai, Lin; Li, Huilin

doi:10.1016/j.sbi.2023.102563

Cited by 5 publications

(6 citation statements)

References 52 publications

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“…Those first TMDs efficiently inserted by the EMC, such as those featuring negative charges and short N‐terminal soluble structural domains, enter the bilayer via their hydrophilic vestibule. TMDs not promptly inserted by the EMC are transferred to other insertion enzymes, including TMCO1, and in some cases, Sec61 22,59 …”

Section: The Functions Of Emcmentioning

confidence: 99%

ER membrane complex (EMC): Structure, functions, and roles in diseases

Zhu,

Zhang

2024

The FASEB Journal

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The endoplasmic reticulum (ER) is the largest membrane system in eukaryotic cells and is the primary site for the biosynthesis of lipids and carbohydrates, as well as for the folding, assembly, modification, and transport of secreted and integrated membrane proteins. The ER membrane complex (EMC) on the ER membrane is an ER multiprotein complex that affects the quality control of membrane proteins, which is abundant and widely preserved. Its disruption has been found to affect a wide range of processes, including protein and lipid synthesis, organelle communication, endoplasmic reticulum stress, and viral maturation, and may lead to neurodevelopmental disorders and cancer. Therefore, EMC has attracted the attention of many scholars and become a hot field. In this paper, we summarized the main contributions of the research of EMC in the past nearly 15 years, and reviewed the structure and function of EMC as well as its related diseases. We hope this review will promote further progress of research on EMC.

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Section: The Functions Of Emcmentioning

confidence: 99%

ER membrane complex (EMC): Structure, functions, and roles in diseases

Zhu,

Zhang

2024

The FASEB Journal

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“…The Oxa1 family insertase YidC and the auxiliary SecDF-YajC complex can cooperate with the SecYEG translocon to facilitate insertion 7,8 . The insertion of multipass proteins in eukaryotes is more complex, and was recently shown to involve several additional complexes in the vicinity of Sec61, the eukaryotic SecYEG homolog 9–11 . However, the fundamental principles of cotranslational insertion are conserved across organisms.…”

Section: Mainmentioning

confidence: 99%

“…The Oxa1 family insertase YidC and the auxiliary SecDF-YajC complex can cooperate with the SecYEG translocon to facilitate insertion (Shanmugam & Dalbey, 2019; Troman & Collinson, 2021). The insertion of multipass proteins in eukaryotes is more complex, and was recently shown to involve several additional complexes in the vicinity of Sec61, the eukaryotic SecYEG homolog (Smalinskaite et al, 2022; Sundaram et al, 2022; Bai & Li, 2023). Importantly, when each TM finishes its synthesis, it still resides inside the ribosome exit tunnel, inaccessible to the insertion machinery.…”

Section: Mainmentioning

confidence: 99%

Membrane protein sequence features direct post-translational insertion

Kalinin,

Peled-Zehavi,

Barshap

et al. 2023

Preprint

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The proper folding of multispanning membrane proteins (MPs) hinges on the accurate insertion of their transmembrane helices (TMs) into the membrane. Predominantly, TMs are inserted during protein translation, via a conserved mechanism centered around the Sec translocon. Our study reveals that the C-terminal TMs (cTMs) of numerous MPs across various organisms bypass this cotranslational route, necessitating an alternative posttranslational insertion strategy. We demonstrate that evolution has refined the hydrophilicity and length of these proteins’ C-terminal tails to optimize cTM insertion. Alterations in the C-tail sequence disrupt cTM insertion in bothE. coliand human, leading to protein defects, loss of function, and genetic diseases. InE. coli, we identify YidC, a member of the widespread Oxa1 family, as the insertase facilitating cTMs insertion, with C-tail mutations disrupting the productive interaction of cTMs with YidC. Thus, MP sequences are fine-tuned for effective collaboration with the cellular biogenesis machinery, ensuring proper membrane protein folding.

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“…Hydrophobic interaction is essential during protein folding into an ordered structure with a hydrophilic surface and hydrophobic core. 11,12 Further, the protein recognition of small molecules such as drugs, 13,14 ligand binding with receptors, 15 and enzyme biocatalysis reactions 16,17 oen occur in protein hydrophobic pockets with essential functional hotspots. Recently, studies of structural biology have reported the key binding sites in the hydrophobic pockets of membrane proteins, such as vitamin K epoxide reductases (VKOR) with vitamin K antagonists, 18 ATP-binding cassette (ABD) transporters with inhibitors, 19 and G-protein-coupled receptors (GPCRs) with various ligands.…”

Section: Introductionmentioning

confidence: 99%