Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos.

ABSTRACT: Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export by the formation of tunnel-like connections between the ER and Golgi. Hitherto, cargo-recognition appeared to be mediated by an SH3-like domain. Based on structural and dynamic data as well as interaction studies from NMR spectroscopy and microscale thermophoresis presented here, we show that the luminal cargo-recognition domain of TANGO1 adopts a new functional fold for which we suggest the term MOTH (MIA, Otoraplin, TALI/TANGO1 homology) domain. These MOTH domains, as well as an evolutionary intermediate found in invertebrates, constitute a distinct domain family that emerged from SH3 domains and acquired the ability to bind collagen.

SUBMITTER: Arnolds O

PROVIDER: S-EPMC10119292 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos.

Arnolds Oliver O Stoll Raphael R

Nature communications 20230420 1

Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export by the formation of tunnel-like connections between the ER and Golgi. Hitherto, cargo-recognition appeared to be mediated by an SH3-like domain. Based on structural and dynamic data as well as intera ...[more]

PMID: 37080980

Similar Datasets

A physical mechanism of TANGO1-mediated bulky cargo export.

Project description:The endoplasmic reticulum (ER)-resident protein TANGO1 assembles into a ring around ER exit sites (ERES), and links procollagens in the ER lumen to COPII machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) in the cytoplasm (Raote et al., 2018). Here, we present a theoretical approach to investigate the physical mechanisms of TANGO1 ring assembly and how COPII polymerization, membrane tension, and force facilitate the formation of a transport intermediate for procollagen export. Our results indicate that a TANGO1 ring, by acting as a linactant, stabilizes the open neck of a nascent COPII bud. Elongation of such a bud into a transport intermediate commensurate with bulky procollagens is then facilitated by two complementary mechanisms: (i) by relieving membrane tension, possibly by TANGO1-mediated fusion of retrograde ERGIC membranes and (ii) by force application. Altogether, our theoretical approach identifies key biophysical events in TANGO1-driven procollagen export.

| S-EPMC7704110 | biostudies-literature

TANGO1 and Mia2/cTAGE5 (TALI) cooperate to export bulky pre-chylomicrons/VLDLs from the endoplasmic reticulum.

Project description:Procollagens, pre-chylomicrons, and pre-very low-density lipoproteins (pre-VLDLs) are too big to fit into conventional COPII-coated vesicles, so how are these bulky cargoes exported from the endoplasmic reticulum (ER)? We have shown that TANGO1 located at the ER exit site is necessary for procollagen export. We report a role for TANGO1 and TANGO1-like (TALI), a chimeric protein resulting from fusion of MIA2 and cTAGE5 gene products, in the export of pre-chylomicrons and pre-VLDLs from the ER. TANGO1 binds TALI, and both interact with apolipoprotein B (ApoB) and are necessary for the recruitment of ApoB-containing lipid particles to ER exit sites for their subsequent export. Although export of ApoB requires the function of both TANGO1 and TALI, the export of procollagen XII by the same cells requires only TANGO1. These findings reveal a general role for TANGO1 in the export of bulky cargoes from the ER and identify a specific requirement for TALI in assisting TANGO1 to export bulky lipid particles.

| S-EPMC4862334 | biostudies-literature

Fold Evolution before LUCA: Common Ancestry of SH3 Domains and OB Domains.

Project description:SH3 and OB are the simplest, oldest, and most common protein domains within the translation system. SH3 and OB domains are β-barrels that are structurally similar but are topologically distinct. To transform an OB domain to a SH3 domain, β-strands must be permuted in a multistep and evolutionarily implausible mechanism. Here, we explored relationships between SH3 and OB domains of ribosomal proteins, initiation, and elongation factors using a combined sequence- and structure-based approach. We detect a common core of SH3 and OB domains, as a region of significant structure and sequence similarity. The common core contains four β-strands and a loop, but omits the fifth β-strand, which is variable and is absent from some OB and SH3 domain proteins. The structure of the common core immediately suggests a simple permutation mechanism for interconversion between SH3 and OB domains, which appear to share an ancestor. The OB domain was formed by duplication and adaptation of the SH3 domain core, or vice versa, in a simple and probable transformation. By employing the folding algorithm AlphaFold2, we demonstrated that an ancestral reconstruction of a permuted SH3 sequence folds into an OB structure, and an ancestral reconstruction of a permuted OB sequence folds into a SH3 structure. The tandem SH3 and OB domains in the universal ribosomal protein uL2 share a common ancestor, suggesting that the divergence of these two domains occurred before the last universal common ancestor.

| S-EPMC8557408 | biostudies-literature

Tango1 spatially organizes ER exit sites to control ER export.

Project description:Exit of secretory cargo from the endoplasmic reticulum (ER) takes place at specialized domains called ER exit sites (ERESs). In mammals, loss of TANGO1 and other MIA/cTAGE (melanoma inhibitory activity/cutaneous T cell lymphoma-associated antigen) family proteins prevents ER exit of large cargoes such as collagen. Here, we show that Drosophila melanogaster Tango1, the only MIA/cTAGE family member in fruit flies, is a critical organizer of the ERES-Golgi interface. Tango1 rings hold COPII (coat protein II) carriers and Golgi in close proximity at their center. Loss of Tango1, present at ERESs in all tissues, reduces ERES size and causes ERES-Golgi uncoupling, which impairs secretion of not only collagen, but also all other cargoes we examined. Further supporting an organizing role of Tango1, its overexpression creates more and larger ERESs. Our results suggest that spatial coordination of ERES, carrier, and Golgi elements through Tango1's multiple interactions increases secretory capacity in Drosophila and allows secretion of large cargo.

| S-EPMC5379956 | biostudies-literature

Dual function for Tango1 in secretion of bulky cargo and in ER-Golgi morphology.

Project description:Tango1 enables ER-to-Golgi trafficking of large proteins. We show here that loss of Tango1, in addition to disrupting protein secretion and ER/Golgi morphology, causes ER stress and defects in cell shape. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect. If large cargos like Dumpy, which we identify as a Tango1 cargo, are removed from the cell, nonbulky proteins reenter the secretory pathway. Removal of blocking cargo also restores cell morphology and attenuates the ER-stress response. Thus, failures in the secretion of nonbulky proteins, ER stress, and defective cell morphology are secondary consequences of bulky cargo retention. By contrast, ER/Golgi defects in Tango1-depleted cells persist in the absence of bulky cargo, showing that they are due to a secretion-independent function of Tango1. Therefore, maintenance of ER/Golgi architecture and bulky cargo transport are the primary functions for Tango1.

| S-EPMC5715762 | biostudies-literature

Identification of CRM1-dependent Nuclear Export Cargos Using Quantitative Mass Spectrometry.

Project description:Chromosome region maintenance 1/exportin1/Exp1/Xpo1 (CRM1) is the major transport receptor for the export of proteins from the nucleus. It binds to nuclear export signals (NESs) that are rich in leucines and other hydrophobic amino acids. The prediction of NESs is difficult because of the extreme recognition flexibility of CRM1. Furthermore, proteins can be exported upon binding to an NES-containing adaptor protein. Here we present an approach for identifying targets of the CRM1-export pathway via quantitative mass spectrometry using stable isotope labeling with amino acids in cell culture. With this approach, we identified >100 proteins from HeLa cells that were depleted from cytosolic fractions and/or enriched in nuclear fractions in the presence of the selective CRM1-inhibitor leptomycin B. Novel and validated substrates are the polyubiquitin-binding protein sequestosome 1, the cancerous inhibitor of protein phosphatase 2A (PP2A), the guanine nucleotide-binding protein-like 3-like protein, the programmed cell death protein 2-like protein, and the cytosolic carboxypeptidase 1 (CCP1). We identified a functional NES in CCP1 that mediates direct binding to the export receptor CRM1. The method will be applicable to other nucleocytoplasmic transport pathways, as well as to the analysis of nucleocytoplasmic shuttling proteins under different growth conditions.

| S-EPMC3591659 | biostudies-literature

SH3 domains: modules of protein-protein interactions.

Project description:Src homology 3 (SH3) domains are involved in the regulation of important cellular pathways, such as cell proliferation, migration and cytoskeletal modifications. Recognition of polyproline and a number of noncanonical sequences by SH3 domains has been extensively studied by crystallography, nuclear magnetic resonance and other methods. High-affinity peptides that bind SH3 domains are used in drug development as candidates for anticancer treatment. This review summarizes the latest achievements in deciphering structural determinants of SH3 function.

| S-EPMC5418429 | biostudies-literature

New approaches to high-throughput structure characterization of SH3 complexes: the example of Myosin-3 and Myosin-5 SH3 domains from S. cerevisiae.

Project description:SH3 domains are small protein modules that are involved in protein-protein interactions in several essential metabolic pathways. The availability of the complete genome and the limited number of clearly identifiable SH3 domains make the yeast Saccharomyces cerevisae an ideal proteomic-based model system to investigate the structural rules dictating the SH3-mediated protein interactions and to develop new tools to assist these studies. In the present work, we have determined the solution structure of the SH3 domain from Myo3 and modeled by homology that of the highly homologous Myo5, two myosins implicated in actin polymerization. We have then implemented an integrated approach that makes use of experimental and computational methods to characterize their binding properties. While accommodating their targets in the classical groove, the two domains have selectivity in both orientation and sequence specificity of the target peptides. From our study, we propose a consensus sequence that may provide a useful guideline to identify new natural partners and suggest a strategy of more general applicability that may be of use in other structural proteomic studies.

| S-EPMC2242487 | biostudies-literature

Structural basis for ubiquitin recognition by SH3 domains.

Project description:The SH3 domain is a protein-protein interaction module commonly found in intracellular signaling and adaptor proteins. The SH3 domains of multiple endocytic proteins have been recently implicated in binding ubiquitin, which serves as a signal for diverse cellular processes including gene regulation, endosomal sorting, and protein destruction. Here we describe the solution NMR structure of ubiquitin in complex with an SH3 domain belonging to the yeast endocytic protein Sla1. The ubiquitin binding surface of the Sla1 SH3 domain overlaps substantially with the canonical binding surface for proline-rich ligands. Like many other ubiquitin-binding motifs, the SH3 domain engages the Ile44 hydrophobic patch of ubiquitin. A phenylalanine residue located at the heart of the ubiquitin-binding surface of the SH3 domain serves as a key specificity determinant. The structure of the SH3-ubiquitin complex explains how a subset of SH3 domains has acquired this non-traditional function.

| S-EPMC2034316 | biostudies-literature

A distant TANGO1 family member promotes vitellogenin export from the ER in <i>C. elegans</i>.

Project description:Vitellogenin is thought to share a common ancestor with human apolipoprotein B (ApoB) for systemic lipid transport. In Caenorhabditis elegans, although a general route for inter-tissue vitellogenin transport has been described, the full mechanism that underlies its intracellular trafficking within the intestine remains obscure. In humans, the TANGO1 family of proteins generates membrane carriers to accommodate bulky ApoB-containing lipoprotein particles for their endoplasmic reticulum (ER) export. TANGO1 orthologs have hitherto been discovered in most metazoans, except nematodes. Here, we report the C. elegans TNGL-1 as a mediator of vitellogenin export from the ER. Depletion of TNGL-1 causes the retention of vitellogenin in the ER lumen. Furthermore, the TNGL-1 C-terminal unstructured domain and its luminal globular domain are required for its proper localization and cargo engagement, respectively. Our findings support TNGL-1 as a distant TANGO1 family member and point to the universal requirement of TANGO1-based mechanisms for the secretion of specific metazoan proteins.

| S-EPMC11841073 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data