Structural and thermodynamic analyses of human TMED1 (p24γ1) Golgi dynamics

Mota, Danielly C.A.M.; Cardoso, Iara Aimê; Mori, Renan M.; Batista, Mariana; Basso, Luis G.M.; Nonato, Maria Cristina; Costa-Filho, Antonio J.; Mendes, Luis Felipe Santos

doi:10.1016/j.biochi.2021.10.002

Cited by 10 publications

(17 citation statements)

References 77 publications

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“…3B). It shows the structural organization of a b-sandwich fold composed of two four-strand antiparallel b-sheets with a conserved disulphide bond bridging b-2 and b-7 strands [38,41,42] (Fig. 3C).…”

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

“…A high tendency for homo-oligomerization, apparently involving the coiled-coil motif in most TMEDs/p24 members, was observed in vivo [43]. Mota et al showed that the isolated TMED1 GOLD domain coexists as a dynamic equilibrium monomer-dimer regulated by ionic strength [42]. Molecular dynamics studies showed that the proposed TMED1 GOLD dimer structure is enthalpically stabilized by approximately À28 kcalÁmol À1 [42].…”

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

“…Mota et al showed that the isolated TMED1 GOLD domain coexists as a dynamic equilibrium monomer-dimer regulated by ionic strength [42]. Molecular dynamics studies showed that the proposed TMED1 GOLD dimer structure is enthalpically stabilized by approximately À28 kcalÁmol À1 [42]. Besides, most of the key residues involved in the dimerization are conserved in the csubfamily [42].…”

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

“…This observation brings a model for the membrane orientation where the negatively charged surface of TMED1 and TMED5 GOLD would remain exposed to the cytosol during their traffic in the early secretory pathway. At the same time, the concave side would face the negatively charged membranes of the Golgi and the ER, enriched in anionic lipids including phosphatidylinositol and sphingolipids [41,42,44].…”

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

“…3C). Interestingly, dimer‐like structures were observed in the crystal packing of TMED1, 5 and 10, with the oligomerization occurring via similar direct interactions involving β1 and β2 strands [38,41,42]. A high tendency for homo‐oligomerization, apparently involving the coiled‐coil motif in most TMEDs/p24 members, was observed in vivo [43].…”

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

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A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities

Mendes

Costa-Filho

2022

FEBS Letters

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The classical secretory pathway is the key membrane-based delivery system in eukaryotic cells. Several families of proteins involved in the secretory pathway, with functionalities going from cargo sorting receptors to the maintenance and dynamics of secretory organelles, share soluble globular domains predicted to mediate protein-protein interactions. One of them is the 'Golgi Dynamics' (GOLD) domain, named after its strong association with the Golgi apparatus. There are many GOLD-containing protein families, such as the transmembrane emp24 domain-containing proteins (TMED/p24 family), animal SEC14-like proteins, human Golgi resident protein ACBD3, a splice variant of TICAM2 called TRAM with GOLD domain, and FYCO1. Here, we critically review the state-of-the-art knowledge of the structures and functions of the main representatives of GOLD-containing proteins in vertebrates. We provide the first unified description of the GOLD domain structure across different families since the first high-resolution structure was determined. With a brand-new update on the definition of the GOLD domain, we also discuss how its tertiary structure fits the b-sandwich-like fold map and give exciting new directions for forthcoming studies.

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Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

Section: The Transmembrane Emp24 Domain (Tmed)/p24 Familymentioning

confidence: 99%

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A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities

Mendes

Costa-Filho

2022

FEBS Letters

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OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization

Ahdritz,

Bouatta,

Floristean

et al. 2024

Nat Methods

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Characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel ligand as a potential drug candidate

Freire

Basso

Mendes

et al. 2022

Sci Rep

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Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective therapeutic strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-dependent RNA-polymerase (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified as a strong ligand of the nsp4-CHIKV and mapped to bind to its active site. The antiviral activity of LabMol-309 was evaluated in cellular-based assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights the biophysical features of nsP4-CHIKV and identifies a new compound as a promising antiviral agent against CHIKV infection.

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Structural and thermodynamic analyses of human TMED1 (p24γ1) Golgi dynamics

Cited by 10 publications

References 77 publications

A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities

A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities

OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization

Characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel ligand as a potential drug candidate

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