Dynamics and Metal Exchange Properties of C4C4 RING Domains from CNOT4 and the p44 Subunit of TFIIH

Houben, Klaartje; Wasielewski, Emeric; Dominguez, Cyril; Kellenberger, Esther; Atkinson, R. Andrew; Timmers, H. Th. Marc; Kieffer, Bruno; Boelens, Rolf

doi:10.1016/j.jmb.2005.04.007

Cited by 21 publications

(20 citation statements)

References 67 publications

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“…The structure contains a large number of hydrogen bonds, including a number of NH-S hydrogen bonds between backbone NH groups and S ␥ atoms of cysteines coordinating zinc ions. These NH-S bonds correlate well with NH groups with large chemical shift perturbations on Cd 2ϩ /Zn 2ϩ exchange, a relationship that has been noted previously (57). Hydrogen 2).…”

Section: Discussionsupporting

confidence: 83%

Solution Structure of RING Finger-like Domain of Retinoblastoma-binding Protein-6 (RBBP6) Suggests It Functions as a U-box

Kappo

Ab²,

Hassem

et al. 2012

Journal of Biological Chemistry

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Background: U-box-containing proteins cooperate with chaperones in ubiquitinating irreversibly unfolded proteins. Results: Retinoblastoma binding protein-6 (RBBP6) contains a zinc-binding U-box-like domain and interacts directly with chaperones. Conclusion: RBBP6 may play a role in protein quality control. Significance: U-boxes should be classified in terms of their interaction with chaperones and not their zinc binding properties.

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Section: Discussionsupporting

confidence: 83%

Solution Structure of RING Finger-like Domain of Retinoblastoma-binding Protein-6 (RBBP6) Suggests It Functions as a U-box

Kappo

Ab²,

Hassem

et al. 2012

Journal of Biological Chemistry

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“…15 N NMR relaxation experiments did not show any significant differences anywhere in the domain (data not shown), but this is not inconsistent, because metal exchange processes take place on timescales much too slow to influence 15 N relaxation rates [time scales of minutes to hours have been reported for Zn-Cd exchange in other zinc fingers (20)]. The poor local order for residues 51-55 ( Fig.…”

Section: Resultsmentioning

confidence: 79%

Solution structure of the U2 snRNP protein Rds3p reveals a knotted zinc-finger motif

Roon

Loening

Obayashi

et al. 2008

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

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Rds3p, a component of the U2 snRNP subcomplex SF3b, is essential for pre-mRNA splicing and is extremely well conserved in all eukaryotic species. We report here the solution structure of Rds3p, which reveals an unusual knotted fold unrelated to previously known knotted proteins. Rds3p has a triangular shape with a GATA-like zinc finger at each vertex. Pairs of cysteines contributing to each finger are arranged nonsequentially in a permuted arrangement reminiscent of domain-swapping but which here involves segments of subdomains within a single chain. We suggest that the structure arose through a process of segment swapping after gene duplication. The fingers are connected through ␤-strands and loops, forming an overall topology strongly resembling a ''triquetra knot.'' The conservation and surface properties of Rds3p suggest that it functions as a platform for protein assembly within the multiprotein SF3b complex of U2 snRNP. The recombinant protein used for structure determination is biologically active, as it restores splicing activity in a yeast splicing extract depleted of native Rds3p.knot ͉ NMR ͉ splicing

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“…Reduced Spectral Density Analyses-The R 1 and R 2 relaxation rates and hetero-nuclear steady state { 1 H}-{ 15 N} NOEs were analyzed by reduced spectral density mapping (44,45), under the assumption that the spectral density functions at high frequency are equal as follows: …”

Section: Expression Purification and Nmr Sample Preparation Of Epacmentioning

confidence: 99%

Dynamically Driven Ligand Selectivity in Cyclic Nucleotide Binding Domains

Das

Chowdhury

Mazhab-Jafari

et al. 2009

Journal of Biological Chemistry

100

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One of the mechanisms that minimize the aberrant cross-talk between cAMP-and cGMP-dependent signaling pathways relies on the selectivity of cAMP binding domains (CBDs). For instance, the CBDs of two critical eukaryotic cAMP receptors, i.e. protein kinase A (PKA) and the exchange protein activated by cAMP (EPAC), are both selectively activated by cAMP. However, the mechanisms underlying their cAMP versus cGMP selectivity are quite distinct. In PKA this selectivity is controlled mainly at the level of ligand affinity, whereas in EPAC it is mostly determined at the level of allostery. Currently, the molecular basis for these different selectivity mechanisms is not fully understood. We have therefore comparatively analyzed by NMR the cGMP-bound states of the essential CBDs of PKA and EPAC, revealing key differences between them. Specifically, cGMP binds PKA preserving the same syn base orientation as cAMP at the price of local steric clashes, which lead to a reduced affinity for cGMP. Unlike PKA, cGMP is recognized by EPAC in an anti conformation and generates several short and long range perturbations. Although these effects do not alter significantly the structure of the EPAC CBD investigated, remarkable differences in dynamics between the cAMP-and cGMP-bound states are detected for the ionic latch region. These observations suggest that one of the determinants of cGMP antagonism in EPAC is the modulation of the entropic control of inhibitory interactions and illustrate the pivotal role of allostery in determining signaling selectivity as a function of dynamic changes, even in the absence of significant affinity variations.In eukaryotes, protein kinase A (PKA) 2 and the exchange protein directly activated by cAMP (EPAC) are two major receptors for the cAMP second messenger (1-4). The activities of both PKA and EPAC are modulated in a cAMP-dependent manner through cAMP binding domains (CBDs) (1-4). In all isoforms of PKA, two tandem CBDs, denoted as CBD-A and CBD-B, are part of the regulatory subunit (R), in which they are preceded by an N-terminal dimerization docking module and a linker region (Fig. 1a) (1, 3). In the inactive state PKA exists as a tetrameric holo-enzyme complex, including two regulatory (R) subunits and two catalytic (C) subunits (1, 3). Binding of cAMP to the CBDs of the R subunits results in the release of the C subunits and in the activation of the kinase function (1, 3).Unlike PKA, EPAC is a single-chain protein that functions as a guanine nucleotide-exchange factor (GEF) for the small GTPase Rap1 and Rap2 (2, 4). The domain organization of EPAC includes an N-terminal regulatory region (RR) and a C-terminal catalytic region (CR) (Fig. 1b). There are two known homologous isoforms of EPAC, i.e. EPAC1 and EPAC2. One of the key differences between EPAC1 and EPAC2 is that in the former there is only a single CBD, whereas in the latter there are two noncontiguous CBDs, i.e. CBD-A and CBD-B. However, CBD-A has been shown not to be strictly necessary for the cAMP-dependent activation of EPAC (2, 4)....

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Dynamics and Metal Exchange Properties of C4C4 RING Domains from CNOT4 and the p44 Subunit of TFIIH

Cited by 21 publications

References 67 publications

Solution Structure of RING Finger-like Domain of Retinoblastoma-binding Protein-6 (RBBP6) Suggests It Functions as a U-box

Solution Structure of RING Finger-like Domain of Retinoblastoma-binding Protein-6 (RBBP6) Suggests It Functions as a U-box

Solution structure of the U2 snRNP protein Rds3p reveals a knotted zinc-finger motif

Dynamically Driven Ligand Selectivity in Cyclic Nucleotide Binding Domains

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