N-Terminal Segments Modulate the α-Helical Propensities of the Intrinsically Disordered Basic Regions of bZIP Proteins

Das, Rahul K.; Crick, Scott L.; Pappu, Rohit V.

doi:10.1016/j.jmb.2011.12.043

Cited by 59 publications

(64 citation statements)

References 62 publications

(100 reference statements)

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“…This is supported by experiments showing that the N-terminal domain of HY5 undergoes a-helical folding induced by TFE (Yoon et al, 2006), and this potential MoRF overlaps with the region in HY5 (residues from 25 to 60) that binds to COP1 (Hardtke et al, 2000). Potential MoRFs have also been suggested to exist in the basic regions of 15 different bZIPs (Das et al, 2012). Since one of the major functional advantages of IDPs is their ability to interact specifically with multiple molecular targets, it is not surprising that intrinsically disordered TFs are prime candidates for being the crucial hub proteins or building blocks upon which flexible networks have evolved to exert fine-tuned transcriptional control over signaling pathways, through specific binding-induced folding of various MoRFs in the TRDs ( Figure 2B).…”

Section: Bzip Familymentioning

confidence: 80%

“…A study of conformational ensembles for 15 different bZIPs proposed that the basic regions of the bZIPs have quantifiable preferences for a-helical conformations in their unbound monomeric forms and this helicity varies from one basic region to another despite significant sequence similarity of the bZIP domains. Intramolecular interactions between basic regions and an eight-residue segment directly N-terminal to the basic regions are the primary modulators of helicity in the basic regions (Das et al, 2012). The bZIP HY5 from Arabidopsis positively regulates plant photomorphogenesis through light-dependent regulation of transcription from promoters that contain a G-box, one of several lightresponsive elements.…”

Section: Bzip Familymentioning

confidence: 99%

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Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

et al. 2013

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Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes. Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs. Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein-protein interactions. Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners. In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs. Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development. Based on the roles of disorder in the protein-protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways.

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Section: Bzip Familymentioning

confidence: 80%

Section: Bzip Familymentioning

confidence: 99%

Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

et al. 2013

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“…To be able to answer these types of questions, we present a framework for sequence-ensemble relationships of polyampholytic IDPs that is based on results from atomistic Metropolis Monte Carlo simulations. We use the ABSINTH (self-assembly of biomolecules studied by an implicit, novel, and tunable Hamiltonian) implicit solvation model and force field paradigm (17), a combination that has yielded verifiably accurate results for other IDPs (7,18). We introduce a patterning parameter κ to distinguish between different sequence variants based on the linear sequence distributions of oppositely charged residues.…”

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confidence: 99%

Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues

Das

Pappu

2013

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

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1,307

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The functions of intrinsically disordered proteins (IDPs) are governed by relationships between information encoded in their amino acid sequences and the ensembles of conformations that they sample as autonomous units. Most IDPs are polyampholytes, with sequences that include both positively and negatively charged residues. Accordingly, we focus here on the sequenceensemble relationships of polyampholytic IDPs. The fraction of charged residues discriminates between weak and strong polyampholytes. Using atomistic simulations, we show that weak polyampholytes form globules, whereas the conformational preferences of strong polyampholytes are determined by a combination of fraction of charged residues values and the linear sequence distributions of oppositely charged residues. We quantify the latter using a patterning parameter κ that lies between zero and one. The value of κ is low for well-mixed sequences, and in these sequences, intrachain electrostatic repulsions and attractions are counterbalanced, leading to the unmasking of preferences for conformations that resemble either self-avoiding random walks or generic Flory random coils. Segregation of oppositely charged residues within linear sequences leads to high κ-values and preferences for hairpin-like conformations caused by long-range electrostatic attractions induced by conformational fluctuations. We propose a scaling theory to explain the sequence-encoded conformational properties of strong polyampholytes. We show that naturally occurring strong polyampholytes have low κ-values, and this feature implies a selection for random coil ensembles. The design of sequences with different κ-values demonstrably alters the conformational preferences of polyampholytic IDPs, and this ability could become a useful tool for enabling direct inquiries into connections between sequence-ensemble relationships and functions of IDPs. I ntrinsically disordered proteins (IDPs) feature prominently in proteins associated with transcriptional regulation and signal transduction (1, 2). IDPs fail to fold autonomously, their sequences are deficient in hydrophobic groups and enriched in polar and charged residues (3), and the thermodynamics and kinetics of coupled folding and binding are linked to the intrinsic conformational properties of IDPs (4-12).IDP sequences include both types of charges, and at least 75% of known IDPs are polyampholytes (13). Coarse-grain parameters that are relevant for describing polyampholytes include the fraction of charged residues (FCR) and net charge per residue (NCPR), which are defined as FCR = (f + + f − ) and NCPR = j f + − f − j, where f + and f − denote the fractions of positive and negatively charges, respectively. Polyampholytes are either strong (FCR ≥ 0.3) or weak (FCR < 0.3) and can be neutral (NCPR ∼ 0) or have a net charge. Single molecule measurements have been used to measure the dimensions of three different polyampholytic systems (8), and a mean field model (14) that requires only FCR, NCPR, and the Debye length as inputs was successful...

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“…DNA is shown in a form of a cartoon in atomic colours in all three panels proximal region of bZIP factors contains a canonical basic region involved in DNA binding and nuclear import, while the distal part of bZIP factors carries a leucine dimerisation motif which is known as a leucine zipper. Experimental evidence suggests that the basic regions of bZIP TFs (bZIP-bRs) are necessary and sufficient for DNA binding and specificity (Das et al 2012). Further, it has been suggested through bioinformatic predictions and spectroscopic studies of bZIP-bRs that unbound monomeric bZIP-bRs were uniformly disordered as isolated domains (Das et al 2012).…”

Section: Basic Leucine Zipper Transcription Factorsmentioning

confidence: 99%

“…Experimental evidence suggests that the basic regions of bZIP TFs (bZIP-bRs) are necessary and sufficient for DNA binding and specificity (Das et al 2012). Further, it has been suggested through bioinformatic predictions and spectroscopic studies of bZIP-bRs that unbound monomeric bZIP-bRs were uniformly disordered as isolated domains (Das et al 2012). The bZIP factors bind DNA as dimers, formed by the interaction of two α-helical stretches, consisting of seven amino acid residues per DNA turn (Fig.…”

Section: Basic Leucine Zipper Transcription Factorsmentioning

confidence: 99%

Enhancing Abiotic Stress Tolerance in Plants by Modulating Properties of Stress Responsive Transcription Factors

Hrmová

Lopato

2013

Genomics of Plant Genetic Resources

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Drought, heat and other abiotic stresses negatively impact growth, development, yield and seed quality of plants. The perception of stress and later adaptation to it occurs via signal transduction pathways that regulate expression of stress-responsive genes. Products of these genes include proteins that are directly involved in plant protection and those that fulfill regulatory function. The latter group includes transcription factors (TFs) and other transcription-related proteins that are investigated using the tools of forward and reverse genetics. Genomics analyses also revealed the importance of other proteins such as protein kinases and phosphatases, enzymes involved in metabolism of phospholipids, signalling molecules, etc. Once the stress response pathways are described, the role of key players in these pathways can be optimised through allele mining, selection and genetic engineering. These approaches offer alternatives to classical breeding and marker-assisted selection.During plant responses to drought, a set of basic leucine zipper (bZIP), homeodomain-leucine zipper (HD-Zip) and WRKY TFs are transcriptionally or post-translationally activated via abscisic acid (ABA)-dependent signal transduction pathways. Despite a surge of data on the significance of plant bZIP, HD-Zip and WRKY TFs in the regulation of drought responses, the three-dimensional (3D) structures of these classes of TFs have been poorly defined. This structural information can be used for rational design of variant TFs that can help in understanding their oligomerisation and post-translational modification patterns, as well as their abilities to recognise target DNA sequences. In turn, this knowledge would permit the commercial application of genetically engineered TFs in agricultural biotechnology, by expression of TF variants and using the wild-type or modified promoter regions of stress-responsive genes. To this end, the aim of this review is to discuss strategies for improving tolerance of cereals to drought and other environmental stresses using molecular variants of the abiotic stress responsive TFs.M. Hrmova ( ) · S. Lopato

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N-Terminal Segments Modulate the α-Helical Propensities of the Intrinsically Disordered Basic Regions of bZIP Proteins

Cited by 59 publications

References 62 publications

Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues

Enhancing Abiotic Stress Tolerance in Plants by Modulating Properties of Stress Responsive Transcription Factors

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