A pseudoatomic model of the COPII cage obtained from cryo-electron microscopy and mass spectrometry

Noble, Alex J.; Zhang, Qian; O’Donnell, Jason; Hariri, Hanaa; Bhattacharya, Nilakshee; Marshall, Alan G.; Stagg, Scott M.

doi:10.1038/nsmb.2467

Cited by 60 publications

(72 citation statements)

References 42 publications

(58 reference statements)

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“…This same study also revealed that the Sec23/24 cargo adaptor assembled into a regular lattice on the membrane surface [48] . Taken together, the findings from this and earlier work [43, 44, 49, 46, 47] indicate that the COPII coat can adopt a variety of geometries to accommodate a range of vesicle sizes, with the Sec23/24 adaptor itself playing an unexpected structural role in determining vesicle shape [48] .…”

Section: Copii Coat Assembly May Accommodate Different Cargo Sizessupporting

confidence: 59%

“…Although the polyhedral cage-like structure of the Sec13/31 scaffold surrounding vesicles is well characterized [42–47] , a recent cryo-EM structure of complete COPII complexes assembled on membrane tubules uncovered an alternative cylindrical architecture adopted by this scaffold [48] . This same study also revealed that the Sec23/24 cargo adaptor assembled into a regular lattice on the membrane surface [48] .…”

Section: Copii Coat Assembly May Accommodate Different Cargo Sizesmentioning

confidence: 99%

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Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Paczkowski¹,

Richardson

Fromme

2015

Trends in Cell Biology

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Cargo adaptors sort transmembrane protein cargos into nascent vesicles by binding directly to their cytosolic domains. Recent studies have revealed previously unappreciated roles for cargo adaptors and regulatory mechanisms governing their function. The AP-1 and AP-2 clathrin adaptors switch between open and closed conformations that ensure they function at the right place at the right time. The exomer cargo adaptor plays a direct role in remodeling the membrane for vesicle fission. Several different cargo adaptors functioning in distinct trafficking pathways at the Golgi are similarly regulated through bivalent binding to the Arf1 GTPase, potentially enabling regulation by a threshold concentration of Arf1. Taken together, these studies highlight that cargo adaptors do more than just adapt cargos.

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Section: Copii Coat Assembly May Accommodate Different Cargo Sizessupporting

confidence: 59%

Section: Copii Coat Assembly May Accommodate Different Cargo Sizesmentioning

confidence: 99%

Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Paczkowski¹,

Richardson

Fromme

2015

Trends in Cell Biology

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“…Structural studies have established that the adaptability of the COPII coat (i.e., the capacity to adopt vesicular and tubular forms) depends on two molecular features: variable angles at the vertex, and centrally along the edge, of the Sec13/31 cage; and a flexible (unstructured) polypeptide connection between the inner and outer coat proteins (17,22,25). The variable angles enable the Sec13/31 assembly unit to adapt to cages of different curvature (in two dimensions), and the flexible link between Sec23/24•Sar1 and Sec13/31 allows for variation in the geometric relationship between the inner and outer coat proteins (17).…”

Section: Discussionmentioning

confidence: 99%

TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats

Goldberg

2016

Proc. Natl. Acad. Sci. U.S.A.

101

159

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The supramolecular cargo procollagen is loaded into coat protein complex II (COPII)-coated carriers at endoplasmic reticulum (ER) exit sites by the receptor molecule TANGO1/cTAGE5. Electron microscopy studies have identified a tubular carrier of suitable dimensions that is molded by a distinctive helical array of the COPII inner coat protein Sec23/24•Sar1; the helical arrangement is absent from canonical COPII-coated small vesicles. In this study, we combined X-ray crystallographic and biochemical analysis to characterize the association of TANGO1/cTAGE5 with COPII proteins. The affinity for Sec23 is concentrated in the proline-rich domains (PRDs) of TANGO1 and cTAGE5, but Sec23 recognizes merely a PPP motif. The PRDs contain repeated PPP motifs separated by proline-rich linkers, so a single TANGO1/cTAGE5 receptor can bind multiple copies of coat protein in a close-packed array. We propose that TANGO1/cTAGE5 promotes the accretion of inner coat proteins to the helical lattice. Furthermore, we show that PPP motifs in the outer coat protein Sec31 also bind to Sec23, suggesting that stepwise COPII coat assembly will ultimately displace TANGO1/cTAGE5 and compartmentalize its operation to the base of the growing COPII tubule.vesicle traffic | coat protein | procollagen T he coat protein complex II (COPII)-coated vesicles transport secretory and plasma membrane proteins from the endoplasmic reticulum (ER). COPII vesicle budding involves a stepwise assembly reaction: Membrane-bound Sar1-GTP recruits Sec23/24 to form the inner coat complex that, in turn, recruits the Sec13/31 outer coat protein (1). Sec13/31 self-assembles into a polyhedron, and in the process, it sculpts the ER membrane into a bud, producing a COPII-coated vesicle with a diameter of ∼60 nm (2-4).Small cargo molecules are captured during the budding reaction through mechanisms that are well established (5). However, the formation of canonical 60-nm COPII vesicles cannot explain the packaging of large cargos, such as the procollagen fibril with a length of 300-400 nm. Procollagen follows the conventional route of secretion taken by other extracellular proteins, and its ER export evidently depends on COPII carriers because mutations in genes encoding COPII proteins result in collagen secretion blockade, impaired extracellular matrix deposition, and abnormal craniofacial development (6-8). A key discovery was the identification of the receptor TANGO1 and its coreceptor cTAGE5 as ER-localized machinery for loading procollagen into COPII carriers (9, 10). TANGO1 has a luminal SH3 domain shown to interact with collagen VII and a cytosolic domain that interacts with Sec23/24. Both TANGO1 and cTAGE5 are required for collagen export from the ER (9, 10). The TANGO1 knockout mouse has generalized defects in extracellular matrix formation, owing to a block in ER export of multiple collagen types (11).Recent research has implicated post-ER membranes in TANGO1-mediated carrier formation (12, 13); however, the mechanism of action of TANGO1/cTAGE5 in procollagen export...

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“…At the later stages of assembly, the outer COPII coat component, the Sec13/31 complex, is recruited. Sec13/31 mediates COPII coat flexibility and plays a structural role in promoting the formation of coats of different geometries [9–11]. Finally, newly formed COPII-coated vesicles get pinched off from the ER and are shipped along with the encapsulated cargo to their target destinations [4,5].…”

Section: Introductionmentioning

confidence: 99%

Insights into the Mechanisms of Membrane Curvature and Vesicle Scission by the Small GTPase Sar1 in the Early Secretory Pathway

Hariri¹,

Bhattacharya²,

Johnson³

et al. 2014

Journal of Molecular Biology

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The small GTPase protein Sar1 is known to be involved in both the initiation of COPII coated vesicle formation and scission of the nascent vesicle from the ER. The molecular details for the mechanism of membrane remodeling by Sar1 remain unresolved. Here we show that Sar1 transforms synthetic liposomes into structures of different morphologies including tubules and detached vesicles. We demonstrate that Sar1 alone is competent for vesicle scission in a manner that depends on the concentration of Sar1 molecules occupying the membrane. Sar1 molecules align on low curvature membranes to form an extended lattice. The continuity of this lattice breaks down as the curvature locally increases. The smallest repeating unit constituting the ordered lattice is a Sar1 dimer. The three dimensional structure of the Sar1 lattice was reconstructed by substituting spherical liposomes with galactoceramide lipid tubules of homogeneous diameter. These data suggest that Sar1 dimerization is responsible for the formation of constrictive membrane curvature. We propose a model whereby Sar1 dimers assemble into ordered arrays to promote membrane constriction and COPII-directed vesicle scission.

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A pseudoatomic model of the COPII cage obtained from cryo-electron microscopy and mass spectrometry

Cited by 60 publications

References 42 publications

Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

TANGO1/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats

Insights into the Mechanisms of Membrane Curvature and Vesicle Scission by the Small GTPase Sar1 in the Early Secretory Pathway

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