Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution

Fourniol, Franck J.; Sindelar, Charles V.; Amigues, Béatrice; Clare, Daniel K.; Thomas, Geraint M. H.; Perderiset, Mylène; Francis, Fiona; Houdusse, Anne; Moores, Carolyn A.

doi:10.1083/jcb.201007081

Cited by 119 publications

(153 citation statements)

References 42 publications

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“…However, in all cryo-EM structures of doublecortin bound to 13-protofilament microtubules, only one of the two DCX domains was observed at the corner of four tubulin dimers (8 -10). Even from careful mapping and structural classification of X-linked lissencephaly and subcortical band heterotopia patient mutations onto this structure, the identity of this DCX domain, N-DCX or C-DCX, could not be unambiguously determined (6,8). From these cryo-EM maps at ϳ8 Å resolution, distinction of the structurally similar N-DCX or C-DCX domains by their sequence alone is not possible.…”

Section: Nmr Shows Isolated C-dcx To Assume the DCX Fold Inmentioning

confidence: 99%

“…2). A closed conformation derived from the NMR structure of N-DCX was also used to fit the doublecortin density at the vertex of four tubulin dimers in microtubules observed in cryo-EM (8,10). In PDB entry 5IOI chains A and E, the C-terminal sequence regions are observed in an extended open conformation (Fig.…”

Section: Nmr Shows Isolated C-dcx To Assume the DCX Fold Inmentioning

confidence: 99%

“…Similar experiments showed that single DCX molecules recognize the ends of growing microtubules by their concave lattice curvature and that only patient mutations on C-DCX abolish this (12). These mutations on C-DCX map to the contact sites between the DCX domain and microtubules observed in the cryo-EM reconstructions, suggesting that the bound DCX domain could be C-DCX instead of N-DCX (8,12).…”

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confidence: 99%

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Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies

Burger¹,

Stihle²,

Sharma

et al. 2016

Journal of Biological Chemistry

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Section: Nmr Shows Isolated C-dcx To Assume the DCX Fold Inmentioning

confidence: 99%

Section: Nmr Shows Isolated C-dcx To Assume the DCX Fold Inmentioning

confidence: 99%

mentioning

confidence: 99%

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Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies

Burger¹,

Stihle²,

Sharma

et al. 2016

Journal of Biological Chemistry

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“…Mini microtubule dynamics are regulated by an associated protein, BtubC, leading to stable, cytoskeletal rather than cytomotive filaments. The regulation of mini microtubules by BtubC is reminiscent of what certain microtubule associated proteins (MAPs), such as DCX, Clasp, and Mal3, do to microtubules (21)(22)(23).…”

mentioning

confidence: 99%

Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability

Deng

Fink

Bharat

et al. 2017

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

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Microtubules, the dynamic, yet stiff hollow tubes built from αβ-tubulin protein heterodimers, are thought to be present only in eukaryotic cells. Here, we report a 3.6-Å helical reconstruction electron cryomicroscopy structure of four-stranded mini microtubules formed by bacterial tubulin-like Prosthecobacter dejongeii BtubAB proteins. Despite their much smaller diameter, mini microtubules share many key structural features with eukaryotic microtubules, such as an M-loop, alternating subunits, and a seam that breaks overall helical symmetry. Using in vitro total internal reflection fluorescence microscopy, we show that bacterial mini microtubules treadmill and display dynamic instability, another hallmark of eukaryotic microtubules. The third protein in the btub gene cluster, BtubC, previously known as “bacterial kinesin light chain,” binds along protofilaments every 8 nm, inhibits BtubAB mini microtubule catastrophe, and increases rescue. Our work reveals that some bacteria contain regulated and dynamic cytomotive microtubule systems that were once thought to be only useful in much larger and sophisticated eukaryotic cells.

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“…Here, mutated residues associated with PMG, (ie, the two mutations reported here and the two previously reported) are different from those associated with agyria/pachygyria spectrum and structurally predicted to be involved in lateral interactions between protofilaments, microtubule dynamics or interactions with tubulin partners. Although PMG mutations follow the trend of the majority of other mutations in TUBA1A gene, which predominantly affect surface residues, 29,30 one can hypothesize that phenotypic differences may result from mutation-specific alterations of binding sites with other partners or the function of microtubules themselves. It is worth noticing that the mutation p.Arg390Cys located on a surface residue of the C-terminal region of TUBA1A, and suspected to result in impairments of interactions with partner proteins, leads to two distinct phenotypes: PMG in our series and 'simplified' gyral pattern described in a previous report.…”

Section: One Gene Several Phenotypesmentioning

confidence: 99%

Expanding the spectrum of TUBA1A-related cortical dysgenesis to Polymicrogyria

et al. 2012

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De novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders, ranging from lissencephaly to perisylvian pachygyria. Recently, one family with polymicrogyria (PMG) and mutation in TUBA1A was reported. Hence, the purpose of our study was to determine the frequency of TUBA1A mutations in patients with PMG and better define clinical and imaging characteristics for TUBA1A-related PMG. We collected 95 sporadic patients with non-syndromic bilateral PMG, including 54 with perisylvian PMG and 30 PMG with additional brain abnormalities. Mutation analysis of the TUBA1A gene was performed by sequencing of PCR fragments corresponding to TUBA1A-coding sequences. Three de novo missense TUBA1A mutations were identified in three unrelated patients with PMG representing 3.1% of PMG and 10% of PMGs with complex cerebral malformations. These patients had bilateral perisylvian asymmetrical PMG with dysmorphic basal ganglia cerebellar vermian dysplasia and pontine hypoplasia. These mutations (p.Tyr161His; p.Val235Leu; p.Arg390Cys) appear distributed throughout the primary structure of the alpha-tubulin polypeptide, but their localization within the tertiary structure suggests that PMG-related mutations are likely to impact microtubule dynamics, stability and/or local interactions with partner proteins. These findings broaden the phenotypic spectrum associated with TUBA1A mutations to PMG and further emphasize that additional brain abnormalities, that is, dysmorphic basal ganglia, hypoplastic pons and cerebellar dysplasia are key features for the diagnosis of TUBA1A-related PMG.

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Template-free 13-protofilament microtubule–MAP assembly visualized at 8 Å resolution

Abstract: The high-resolution structure of doublecortin-stabilized microtubules provides unprecedented insight into their in vivo architecture.

Cited by 119 publications

References 42 publications

Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies

Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies

Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability

Expanding the spectrum of TUBA1A-related cortical dysgenesis to Polymicrogyria

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