The design of antiparallel coiled coils

Oakley, Martha G.

doi:10.1016/s0959-440x(00)00232-3

Cited by 136 publications

(111 citation statements)

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“…2c,d). This is somewhat unusual since the majority of coiled-coils observed in protein complexes adopt a parallel orientation 37 . However anti-parallel coiled coils are equally stereochemically favorable.…”

Section: Nmr Structure Of the Smrt-gps2 Complexmentioning

confidence: 99%

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

Oberoi

Fairall

Watson

et al. 2011

Nat Struct Mol Biol

140

156

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Eukaryotic transcriptional repressors function by recruiting large co-regulatory complexes that target histone deacetylase enzymes to gene promoters/enhancers. Transcriptional repression complexes, assembled by the co-repressor NCoR, and its homologue SMRT, play critical roles in many processes including development and metabolic physiology. The core repression complex involves the recruitment of three proteins: HDAC3, GPS2 and TBL1 to a highly conserved repression domain within SMRT and NCoR. We have used a variety of structural and functional approaches to gain insight into the assembly, stoichiometry and biological role of this complex. We report the crystal structure of the tetrameric oligomerization domain of TBL1, which interacts with both SMRT and GPS2, and the NMR structure of the interface complex between GPS2 and SMRT. These structures, together with computational docking, mutagenesis and functional assays, reveal the assembly mechanism and stoichiometry of the co-repressor complex.The regulated repression of transcription plays a key role in many biological processes. These include cell fate decisions during development and cellular differentiation, as well as the maintenance of homeostasis. SMRT and NCoR are large homologous co-repressor proteins that were identified through their role in transcriptional repression by many 5 Corresponding author: john.schwabe@le.ac.uk. 4 These authors should be considered co-first authors. Author ContributionsThe contributions of J.O., L.F. & P.W. were critical to the final manuscript and these authors should be considered co-first authors. J.O. (assisted by J.Gooch) performed most of the protein cloning, expression, purification and interaction mapping, although important preliminary experiments were performed by B.K. J.O. prepared the GPS2-SMRT complex for NMR structure determination which was carried out by J-C.Y. and D.N. Crystallizations were performed primarily by J.O., with some later trials by J.Greenwood and L.F. Crystal structure determinations were performed by L.F., J.O. and J.W.R.S. The interaction motifs in GPS2 and SMRT were identified by J.W.R.S. and tested by pull-down experiments by J.O. Fluorescence polarization, co-immunoprecipitation and co-transfection/ purification assays were performed by P.W. The two-hybrid assays, gel filtrations and NMR comparisons of WT and MT TBL1 were performed by P.W., Z.C. and B.G. In silico docking experiments were performed by T.K. The laboratories of L.N. and D.N. provided experimental expertise for transfection and NMR studies respectively. J.W.R.S. planned and supervised the project and prepared the manuscript with assistance from the other authors. Accession Codes1H, 13C and 15N NMR resonance assignments for the SMRT(167-207) -GPS2(53-90) complex have been deposited at the BioMagResBank under accession code 17271, and the coordinates have been deposited under the pdb accession code 215G. The TBL1 X-ray structures have been deposited with the PDB codes (2XTC, 2XTD & 2XTE). When purified from HeLa cell extr...

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Section: Nmr Structure Of the Smrt-gps2 Complexmentioning

confidence: 99%

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

Oberoi

Fairall

Watson

et al. 2011

Nat Struct Mol Biol

140

156

View full text Add to dashboard Cite

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“…1). Such domains are present in various organisms, and they function in oligomerization processes like the TIR domain [25][26][27]. It should be emphasized that these subfamilies differ not only in terms of the presence or absence of the TIR domain but also in terms of the sequence of the NBS domain [28].…”

Section: The Classification Of Nbs-lrr Proteinsmentioning

confidence: 99%

“…Importantly, the additional host protein, NRIP1, is indispensable for this interaction [48,63,64]. The coiled-coil (CC) domain is composed of two or more α-helices that are usually twisted superhelically around each other in the parallel and antiparallel orientations [25,65]. The domain is usually attributed an analogous role to that of the TIR domain as a mediator in interactions with other elements of the signaling pathways associated with innate immunity.…”

Section: Other Domainsmentioning

confidence: 99%

R proteins as fundamentals of plant innate immunity

Głowacki

Macioszek

Kononowicz

2011

Cellular and Molecular Biology Letters

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Abstract:Plants are attacked by a wide spectrum of pathogens, being the targets of viruses, bacteria, fungi, protozoa, nematodes and insects. Over the course of their evolution, plants have developed numerous defense mechanisms including the chemical and physical barriers that are constitutive elements of plant cell responses locally and/or systemically. However, the modern approach in plant sciences focuses on the evolution and role of plant protein receptors corresponding to specific pathogen effectors. The recognition of an invader's molecules could be in most cases a prerequisite sine qua non for plant survival. Although the predicted three-dimensional structure of plant resistance proteins (R) is based on research on their animal homologs, advanced technologies in molecular biology and bioinformatics tools enable the investigation or prediction of interaction mechanisms for specific receptors with pathogen effectors. Most of the identified R proteins belong to the NBS-LRR family. The presence of other domains (including the TIR domain) apart from NBS and LRR is fundamental for the classification of R proteins into subclasses. Recently discovered additional domains (e.g. WRKY) of R proteins allowed the examination of their localization in plant cells and the role they play in signal transduction during the plant resistance response to biotic stress factors. This review focuses on the current state of knowledge about the NBS-LRR family of plant R proteins: their structure, function and evolution, and the role they play in plant innate immunity.

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“…In contrast, the antiparallel coiled coils, for which rational design principles have only recently been specified (20)(21)(22)(23)(24)(25)(26), are less structurally scrutinized (15,(27)(28)(29)(30). Both configurations play critical roles in biology, acting for example as oligomerization domains, sites of protein/protein recognition, and nucleic acid binding elements (31-33).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,

et al. 2006

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A detailed understanding of the mechanisms by which particular amino acid sequences can give rise to more than one folded structure, such as for proteins that undergo large conformational changes or misfolding, is a long-standing objective of protein chemistry. Here we describe the crystal structures of a single coiled-coil peptide in distinct parallel and antiparallel tetrameric configurations and further describe the parallel or antiparallel crystal structures of several related peptide sequences; the antiparallel tetrameric assemblies represents the first crystal structures of GCN4-derived peptides exhibiting such a configuration. Intriguingly, substitution of a single solvent-exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate the antiparallel configuration, suggesting that the two configurations are close enough in energy for subtle sequence changes to have important structural consequences. We present a structural analysis of the small changes to helix register and side chain conformations that accommodate the two configurations, and have supplemented these results using solution studies and a molecular dynamics energetic analysis using a replica exchange methodology. Considering the previous examples of structural nonspecificity in coiled-coil peptides, the findings reported here not only emphasize the predisposition of the coiled-coil motif to adopt multiple configurations, but also call attention to the associated risk that observed crytstal structures may not represent the only (or even the major) species present in solution.The diverse functional prowess of proteins derives in large part from their ability to adopt unique tertiary and quaternary structures, and a major goal of protein chemistry is thus to understand in detail how primary amino acid sequences specify three-dimensional structures. Conformational changes and protein misfolding are critical events in biological processes and diseases in which a given polypeptide sequence gives rise to more than one folded structure, but detailed structural analyses of such processes are often difficult because multiple † We thank the Skaggs Institute for Chemical Biology for financial support, and NSF for a predoctoral fellowship (L.J.L.). § Coordinates have been deposited in the RCSB Protein Data Bank: peptide 2, 1W5K; E20C (peptide 3), 2CCN; E20S (peptide 4), 2CCE, 2CCF; ABA-pLI (peptide 5), 1W5I; peptide 6, 1W5J; E20C Y17H (peptide 7), 1W5H; E20C Ak (peptide 8), 1W5G.* Address correspondence to this author. (858) 784-2700 (phone); (858) 784-2798 (fax); ghadiri@scripps.edu (e-mail).. ‡ These authors contributed equally to this study.Supporting Information Available. Additional figures, CD wavelength scans, thermal denaturation curves, crystallization statistics. This material is available free of charge via the Internet at http://pubs.acs.org. 1 Abbreviations: ABA, acetamidobenzoic acid; CD, circular dichroism; Cys, cysteine, Glu, glutamic acid; HPLC, high-performance liquid chromatography; Lys, lysine; MALDI-TOF, matr...

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The design of antiparallel coiled coils

Cited by 136 publications

References 72 publications

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

R proteins as fundamentals of plant innate immunity

Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,

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The design of antiparallel coiled coils

Cited by 136 publications

References 72 publications

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery

R proteins as fundamentals of plant innate immunity

Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution,

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Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,