Structural Dynamics and Multiregion Interactions in Dynein-Dynactin Recognition

Morgan, John D.; Song, Yanjun; Barbar, Elisar

doi:10.1074/jbc.m111.296277

Cited by 35 publications

(76 citation statements)

References 49 publications

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“…IC is a 74-kDa protein with a predominantly unstructured N-terminal domain (15) and a WD-rich C-terminal domain. Within the predominantly unstructured N-terminal domain of Drosophila melanogaster IC, residues 3-36 are helical (1), consistent with the coiled-coil secondary structure predicted for residues 1-40 from sequence analysis (16), residues 48 -60 have nascent helical propensity (1), and residues 222-231 constitute a self-association domain (17). The N-terminal domain binds all three light chains.…”

supporting

confidence: 56%

“…Glued (residues 221-509, referred hereafter as p150 CC1 ) followed previously published protocols (1,15,18).…”

Section: Expression and Purification Of Recombinant Nude Proteins-mentioning

confidence: 99%

“…Data were acquired on the p150 CC1 -IC(1-87) complex (molar ratio 3:1), the nNudE-IC(1-87) complex (molar ratio 3:1), the p150 CC1 -IC(1-87) complex titrated with nNudE (molar ratio 3:1:4), and the nNudE-IC(1-87) complex titrated with p150 CC1 (molar ratio 3:1:4). (1,18). The peak corresponding to residue 87 was used as an internal reference to correct for small changes in peak intensities across spectra.…”

Section: Expression and Purification Of Recombinant Nude Proteins-mentioning

confidence: 99%

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Intrinsic Disorder in Dynein Intermediate Chain Modulates Its Interactions with NudE and Dynactin

Nyarko

Song

Barbar

2012

Journal of Biological Chemistry

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supporting

confidence: 56%

“…Glued (residues 221-509, referred hereafter as p150 CC1 ) followed previously published protocols (1,15,18).…”

Section: Expression and Purification Of Recombinant Nude Proteins-mentioning

confidence: 99%

Section: Expression and Purification Of Recombinant Nude Proteins-mentioning

confidence: 99%

See 1 more Smart Citation

Intrinsic Disorder in Dynein Intermediate Chain Modulates Its Interactions with NudE and Dynactin

Nyarko

Song

Barbar

2012

Journal of Biological Chemistry

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“…A domain of IC that includes recognition motifs for light chains Tctex1 and LC8 is, by NMR chemical shift criteria, fully disordered with limited propensity for secondary structure [4, 17]. A high level of disorder is also manifested by negative heteronuclear NOEs [4].…”

Section: Bivalent Idp Duplex Formationmentioning

confidence: 99%

Polybivalency and disordered proteins in ordering macromolecular assemblies

Barbar¹,

Nyarko²

2015

Seminars in Cell & Developmental Biology

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Intrinsically disordered proteins (IDPs) are prevalent in macromolecular assemblies and are thought to mediate protein recognition in complex regulatory processes and signaling pathways. The formation of a polybivalent scaffold is a key process by which IDPs drive early steps in macromolecular assemblies. Three intrinsically disordered proteins, IC, Swallow and Nup159, are core components, respectively, of cytoplasmic dynein, bicoid mRNA localization apparatus, and nuclear pore complexes. In all three systems, the hub protein LC8 recognizes on the IDP, short linear motifs that are fully disordered in the apo form, but adopt a β-strand when bound to LC8. The IDP/LC8 complex forms a bivalent scaffold primed to bind additional bivalent ligands. Scaffold formation also promotes self-association and/or higher order organization of the IDP components at a site distant from LC8 binding. Rigorous thermodynamic analyses imply that association of additional bivalent ligands is driven by entropic effects where the first binding event is weak but subsequent binding of additional ligands occurs with higher affinity. Here, we review specific examples of macromolecular assemblies in which polybivalency of aligned IDP duplexes not only enhances binding affinity and results in formation of a stable complex but also compensates unfavorable steric and enthalpic interactions. We propose that polybivalent scaffold assembly involving IDPs and LC8-like proteins is a general process in the cell biology of a class of multi-protein structures that are stable yet fine-tuned for diverse cellular requirements.

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“…For example, transient disorder within the motor head is proposed to mediate the 8-nm-long steps of kinesin as it ' walks ' along microtubules (Hyeon and Onuchic , 2007 ). Also, the motor protein dynein depends on disorder-order transitions for interactions with transported cargo and other aspects of its function (Morgan et al , 2011 ). Furthermore, the FG-Nup proteins, which occupy the pore of the nuclear pore complex (NPC), form a dynamic, gel-like structure that facilitates passage of adapter-bound cargo through the NPC but otherwise serve as a barrier to macromolecular diffusion (Kriwacki and Yoon , 2011 ).…”

Section: Functional Advantages Of Disordermentioning

confidence: 99%

Disorder-function relationships for the cell cycle regulatory proteins p21 and p27

Mitrea

Yoon²,

Ou³

et al. 2012

BCHM

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The classic structure-function paradigm has been challenged by a recently identifi ed class of proteins: intrinsically disordered proteins (IDPs). Despite their lack of stable secondary or tertiary structure, IDPs are prevalent in all forms of life and perform myriad cellular functions, including signaling and regulation. Importantly, disruption of IDP homeostasis is associated with numerous human diseases, including cancer and neurodegeneration. Despite wide recognition of IDPs, the molecular mechanisms underlying their functions are not fully understood. Here we review the structural features and disorder-function relationships for p21 and p27, two cyclindependent kinase (Cdk) regulators involved in controlling cell division and fate. Studies of p21 bound to Cdk2/cyclin A revealed that a helix stretching mechanism mediates binding promiscuity. Further, investigations of Tyr88-phosphorylated p27 identifi ed a signaling conduit that controls cell division and is disrupted in certain cancers. These mechanisms rely upon a balance between nascent structure in the free state, induced folding upon binding, and persistent fl exibility within functional complexes. Although these disorder-function relationships are likely to be recapitulated in other IDPs, it is also likely that the vocabulary of their mechanisms is much more extensive than is currently understood. Further study of the physical properties of IDPs and elucidation of their links with function are needed to fully understand the mechanistic language of IDPs.

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Structural Dynamics and Multiregion Interactions in Dynein-Dynactin Recognition

Cited by 35 publications

References 49 publications

Intrinsic Disorder in Dynein Intermediate Chain Modulates Its Interactions with NudE and Dynactin

Intrinsic Disorder in Dynein Intermediate Chain Modulates Its Interactions with NudE and Dynactin

Polybivalency and disordered proteins in ordering macromolecular assemblies

Disorder-function relationships for the cell cycle regulatory proteins p21 and p27

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