Coiled Coil Domains: Stability, Specificity, and Biological Implications

Mason, Jody M.; Arndt, Katja M.

doi:10.1002/chin.200415270

Cited by 102 publications

(139 citation statements)

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“…This dimerization is mediated by their coiled-coil domains, domains frequently demonstrated to be important for protein-protein multimerization (4,49). This dimerization has been shown to be important for regulation of F-actin bundling by neurabin.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis for Spinophilin−Neurabin Receptor Interaction

Kelker

Dancheck

et al. 2007

Biochemistry

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Neurabin and spinophilin are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. However, thus far, it is still unknown how neurabin and spinophilin themselves are targeted to these membrane receptors. Spinophilin and neurabin contain a single PDZ domain, a common protein-protein interaction recognition motif, which are 86% identical in sequence. We report the structures of both the neurabin and spinophilin PDZ domains determined using biomolecular NMR spectroscopy. These proteins form the canonical PDZ domain fold. However, despite their high degree of sequence identity, there are distinct and significant structural differences between them, especially between the peptide binding pockets. Using two-dimensional 1 H-15 N HSQC NMR analysis, we demonstrate that C-terminal peptide ligands derived from glutamatergic AMPA and NMDA receptors and cytosolic proteins directly and differentially bind spinophilin and neurabin PDZ domains. This peptide binding data also allowed us to classify the neurabin and spinophilin PDZ domains as the first identified neuronal hybrid class V PDZ domains, which are capable of binding both class I and II peptides. Finally, the ability to bind to glutamate receptor subunits suggests that the PDZ domains of neurabin and spinophilin are important for targeting PP1 to C-terminal phosphorylation sites in AMPA and NMDA receptor subunits.Neurabin (1) and spinophilin (2-4) are neuronal scaffolding proteins that play important roles in synaptic transmission and synaptic plasticity (5, 6). Neurabin and spinophilin are highly enriched in dendritic spines, the site of excitatory neurotransmission. Neurabin is expressed almost exclusively in neuronal cells, while spinophilin is expressed ubiquitously, although it is highly enriched in neurons. Because spinophilin is a ubiquitous isoform of neurabin, it is sometimes termed neurabin II (3). Neurabin consists of 1095 residues (MW ) 122 730 Da), while spinophilin is smaller, consisting of only 817 residues (MW ) 89 640 Da). Figure 1a shows a domain representation for both proteins. As is typical for scaffolding proteins, both proteins contain multiple protein interaction domains. Both neurabin and spinophilin contain an F-actin binding, a PP1-binding, a PDZ, and a C-terminal coiled-coil domain. In addition, neurabin, but not spinophilin [in vertebrates (7)], contains a sterile R motif (SAM) domain in its C-terminus, while spinophilin, but not neurabin, is proposed to have a dopamine receptor-R-adrenergic interacting domain in its N-terminus, possibly between spinophilin residues 200 and 400 (8, 9). The highest level of primary sequence identity between neurabin and spinophilin is found in the PDZ domains (86%), the protein phosphatase 1 (PP1) binding domains (81%), and the coiled-coil domains (63%).Both neurabin and spinophilin have a central role in signali...

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Section: Discussionmentioning

confidence: 99%

Structural Basis for Spinophilin−Neurabin Receptor Interaction

Kelker

Dancheck

et al. 2007

Biochemistry

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“…Important determinants include electrostatic interactions involving e and g sites, packing complementarity of a and d positions, and hydrogen bonding requirements of buried or partially buried polar groups [4,13]. The influence of e/g electrostatics on coiled-coil stability has long been controversial and continues to attract attention [32,33].…”

Section: Uncovering Relationships Between Sequence Structure and Stamentioning

confidence: 99%

“…Reviews have summarized much of the accumulated knowledge regarding coiled coils [1,4,7,13]. Here, we focus on recent results in three areas.…”

Section: Introductionmentioning

confidence: 99%

Structural specificity in coiled-coil interactions

Grigoryan

Keating

2008

Current Opinion in Structural Biology

267

283

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Coiled coils have a rich history in the field of protein design and engineering. Novel structures, such as the first 7-helix coiled coil, continue to provide surprises and insights. Large-scale data sets quantifying the influence of systematic mutations on coiled-coil stability are a valuable new asset to the area. Scoring methods based on sequence and/or structure can predict interaction preferences in coiled-coil-mediated bZIP transcription factor dimerization. Experimental and computational methods for dealing with the near-degeneracy of many coiled-coil structures appear promising for future design applications.

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“…4,5 Coiled coils can form discrete domains within proteins, or direct protein-protein interactions. 6,7 Figure 1. The α-helical coiled coil.…”

Section: Introductionmentioning

confidence: 99%

N@a and N@d: Oligomer and Partner Specification by Asparagine in Coiled-Coil Interfaces

Fletcher¹,

Bartlett²,

Boyle³

et al. 2017

ACS Chem. Biol.

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The α-helical coiled coil is one of the best-studied protein–protein interaction motifs. As a result, sequence-to-structure relationships are available for the prediction of natural coiled-coil sequences and the de novo design of new ones. However, coiled coils adopt a wide range of oligomeric states and topologies, and our understanding of the specification of these and the discrimination between them remains incomplete. Gaps in our knowledge assume more importance as coiled coils are used increasingly to construct biomimetic systems of higher complexity; for this, coiled-coil components need to be robust, orthogonal, and transferable between contexts. Here, we explore how the polar side chain asparagine (Asn, N) is tolerated within otherwise hydrophobic helix–helix interfaces of coiled coils. The long-held view is that Asn placed at certain sites of the coiled-coil sequence repeat selects one oligomer state over others, which is rationalized by the ability of the side chain to make hydrogen bonds, or interactions with chelated ions within the coiled-coil interior of the favored state. We test this with experiments on de novo peptide sequences traditionally considered as directing parallel dimers and trimers, and more widely through bioinformatics analysis of natural coiled-coil sequences and structures. We find that when located centrally, rather than near the termini of such coiled-coil sequences, Asn does exert the anticipated oligomer-specifying influence. However, outside of these bounds, Asn is observed less frequently in the natural sequences, and the synthetic peptides are hyperthermostable and lose oligomer-state specificity. These findings highlight that not all regions of coiled-coil repeat sequences are equivalent, and that care is needed when designing coiled-coil interfaces.

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Coiled Coil Domains: Stability, Specificity, and Biological Implications

Abstract: Biochemistry Biochemistry Z 0250 Coiled Coil Domains: Stability, Specificity, and Biological Implications -[77 refs.]. -(MASON, J. M.; ARNDT*, K. M.; ChemBioChem 5 (2004) 2, 170-176; Inst. Biol. II, Microbiol., Albert-Ludwigs-Univ., D-79104 Freiburg/Br., Germany; Eng.) -Lindner 15-270

Cited by 102 publications

References 1 publication

Structural Basis for Spinophilin−Neurabin Receptor Interaction

Structural Basis for Spinophilin−Neurabin Receptor Interaction

Structural specificity in coiled-coil interactions

N@a and N@d: Oligomer and Partner Specification by Asparagine in Coiled-Coil Interfaces

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