Structural Analysis of Dynein Intermediate and Light Chains

Williams, John C.; Siglin, Amanda E.; Lightcap, Christine M.; Dawn, Amrita

doi:10.1016/b978-0-12-382004-4.10005-6

Cited by 4 publications

(3 citation statements)

References 177 publications

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“…Whereas homodimeric DYNLL binds to dozens of protein targets and, in almost every case (including DIC), a K X TQT or KDTGIQ motif is recognized , no consensus binding sequence for DYNLT when binding to its protein interaction partners has yet been identified. With a growing list, DYNLT binders include over 20 polypeptides of both cellular and viral origin but sequence comparison reveals no clear sequence motif. Moreover, whereas many 3D structures (both from NMR data and protein crystals) of DYNLL in complex with target peptides are available today (see for a recent review), DYNLT seems to be more refractory to structural studies.…”

Section: Introductionmentioning

confidence: 99%

DYNLT (Tctex‐1) forms a tripartite complex with dynein intermediate chain and RagA, hence linking this small GTPase to the dynein motor

et al. 2015

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It has been suggested that DYNLT, a dynein light chain known to bind to various cellular and viral proteins, can function as a microtubule–cargo adaptor. Recent data showed that DYNLT links the small GTPase Rab3D to microtubules and, for this to occur, the DYNLT homodimer needs to display a binding site for dynein intermediate chain together with a binding site for the small GTPase. We have analysed in detail how RagA, another small GTPase, associates to DYNLT. After narrowing down the binding site of RagA to DYNLT we could identify that a β strand, part of the RagA G3 box involved in nucleotide binding, mediates this association. Interestingly, we show that both microtubule‐associated DYNLT and cytoplasmic DYNLT are equally able to bind to the small GTPases Rab3D and RagA. Using NMR spectroscopy, we analysed the binding of dynein intermediate chain and RagA to mammalian DYNLT. Our experiments identify residues of DYNLT affected by dynein intermediate chain binding and residues affected by RagA binding, hence distinguishing the docking site for each of them. In summary, our results shed light on the mechanisms adopted by DYNLT when binding to protein cargoes that become transported alongside microtubules bound to the dynein motor.

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Section: Introductionmentioning

confidence: 99%

DYNLT (Tctex‐1) forms a tripartite complex with dynein intermediate chain and RagA, hence linking this small GTPase to the dynein motor

et al. 2015

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“…All IC homologs possess a conserved WD40 domain in the Cterminus that interacts with HCs (Tynan et al 2000). A secondary structure analysis using Jpred and RONN predicted that the N-terminal region of cytoplasmic IC1 and IC2 comprise coiled coil and highly disordered regions (Williams et al 2012). However, the secondary structure prediction analysis also indicated that the N-terminal region of IC1 is highly disordered but that of IC2 possesses a folded structure in axonemal ICs (Williams et al 2012).…”

Section: Intermediate Chainmentioning

confidence: 99%

Structural atlas of dynein motors at atomic resolution

2018

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Dynein motors are biologically important bio-nanomachines, and many atomic resolution structures of cytoplasmic dynein components from different organisms have been analyzed by X-ray crystallography, cryo-EM, and NMR spectroscopy. This review provides a historical perspective of structural studies of cytoplasmic and axonemal dynein including accessory proteins. We describe representative structural studies of every component of dynein and summarize them as a structural atlas that classifies the cytoplasmic and axonemal dyneins. Based on our review of all dynein structures in the Protein Data Bank, we raise two important points for understanding the two types of dynein motor and discuss the potential prospects of future structural studies.

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“…With a growing list, DYNLT1 binders include over 20 polypeptides of both cellular and viral origin (17,18). So far, no consensus binding sequence for DYNLT1 when binding to its protein partners has yet been identified, and it is not even known whether they associate to the canonical binding groove or to the protein surface.…”

Section: It Has Been Suggested That Dynlt1 a Dynein Light Chain Knowmentioning

confidence: 99%

Molecular Basis for the Protein Recognition Specificity of the Dynein Light Chain DYNLT1/Tctex1

Merino-Gracia

Zamora-Carreras

Bruix

et al. 2016

Journal of Biological Chemistry

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It has been suggested that DYNLT1, a dynein light chain known to bind to various cellular and viral proteins, can function both as a molecular clamp and as a microtubule-cargo adapter. Recent data have shown that the DYNLT1 homodimer binds to two dynein intermediate chains to subsequently link cargo proteins such as the guanine nucleotide exchange factor Lfc or the small GTPases RagA and Rab3D. Although over 20 DYNLT1-interacting proteins have been reported, the exact sequence requirements that enable their association to the canonical binding groove or to the secondary site within the DYNLT1 surface are unknown. We describe herein the sequence recognition properties of the hydrophobic groove of DYNLT1 known to accommodate dynein intermediate chain. Using a pepscan approach, we have substituted each amino acid within the interacting peptide for all 20 natural amino acids and identified novel binding sequences. Our data led us to propose activin receptor IIB as a novel DYNLT1 ligand and suggest that DYNLT1 functions as a molecular dimerization engine bringing together two receptor monomers in the cytoplasmic side of the membrane. In addition, we provide evidence regarding a dual binding mode adopted by certain interacting partners such as Lfc or the parathyroid hormone receptor. Finally, we have used NMR spectroscopy to obtain the solution structure of human DYNLT1 forming a complex with dynein intermediate chain of ∼74 kDa; it is the first mammalian structure available.

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Structural Analysis of Dynein Intermediate and Light Chains

Cited by 4 publications

References 177 publications

DYNLT (Tctex‐1) forms a tripartite complex with dynein intermediate chain and RagA, hence linking this small GTPase to the dynein motor

DYNLT (Tctex‐1) forms a tripartite complex with dynein intermediate chain and RagA, hence linking this small GTPase to the dynein motor

Structural atlas of dynein motors at atomic resolution

Molecular Basis for the Protein Recognition Specificity of the Dynein Light Chain DYNLT1/Tctex1

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