125 research outputs found

    Erratum: Signal propagation in proteins and relation to equilibrium fluctuations (PLoS Computational Biology (2007) 3, 9, (e172) DOI: 10.1371/journal.pcbi.0030172))

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    Elastic network (EN) models have been widely used in recent years for describing protein dynamics, based on the premise that the motions naturally accessible to native structures are relevant to biological function. We posit that equilibrium motions also determine communication mechanisms inherent to the network architecture. To this end, we explore the stochastics of a discrete-time, discrete-state Markov process of information transfer across the network of residues. We measure the communication abilities of residue pairs in terms of hit and commute times, i.e., the number of steps it takes on an average to send and receive signals. Functionally active residues are found to possess enhanced communication propensities, evidenced by their short hit times. Furthermore, secondary structural elements emerge as efficient mediators of communication. The present findings provide us with insights on the topological basis of communication in proteins and design principles for efficient signal transduction. While hit/commute times are information-theoretic concepts, a central contribution of this work is to rigorously show that they have physical origins directly relevant to the equilibrium fluctuations of residues predicted by EN models

    Functional modes of proteins are among the most robust ones

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    It is shown that a small subset of modes which are likely to be involved in protein functional motions of large amplitude can be determined by retaining the most robust normal modes obtained using different protein models. This result should prove helpful in the context of several applications proposed recently, like for solving difficult molecular replacement problems or for fitting atomic structures into low-resolution electron density maps. Moreover, it may also pave the way for the development of methods allowing to predict such motions accurately.Comment: 4 pages, 5 figure

    Markov propagation of allosteric effects in biomolecular systems: application to GroEL–GroES

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    We introduce a novel approach for elucidating the potential pathways of allosteric communication in biomolecular systems. The methodology, based on Markov propagation of ‘information' across the structure, permits us to partition the network of interactions into soft clusters distinguished by their coherent stochastics. Probabilistic participation of residues in these clusters defines the communication patterns inherent to the network architecture. Application to bacterial chaperonin complex GroEL–GroES, an allostery-driven structure, identifies residues engaged in intra- and inter-subunit communication, including those acting as hubs and messengers. A number of residues are distinguished by their high potentials to transmit allosteric signals, including Pro33 and Thr90 at the nucleotide-binding site and Glu461 and Arg197 mediating inter- and intra-ring communication, respectively. We propose two most likely pathways of signal transmission, between nucleotide- and GroES-binding sites across the cis and trans rings, which involve several conserved residues. A striking observation is the opposite direction of information flow within cis and trans rings, consistent with negative inter-ring cooperativity. Comparison with collective modes deduced from normal mode analysis reveals the propensity of global hinge regions to act as messengers in the transmission of allosteric signals

    Crafts and gear used for marine fishing along the Andhra Pradesh coast

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    Until the middle of nineteen sixties fishing for marine finfishes and shellfishes along the Andhra Pradesh coast used to be carried out employing indigenous non-mechanised crafts. Subsequently trawlers and later mechanised vessels operating gillnets came into use which resulted in the increased fish production. Use of outboard engine on indigenous crafts for reaching fishing grounds is a recent feature of near the coast fishing. The different kinds of non-mechanised and mechanised crafts and gear employed in the region are dealt with in this article

    Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain

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    Viral BCL2 proteins (vBCL2s) help to sustain chronic infection of host proteins to inhibit apoptosis and autophagy. However, details of conformational changes in vBCL2s that enable binding to BH3Ds remain unknown. Using all-atom, multiple microsecond-long molecular dynamic simulations (totaling 17 μs) of the murine γ-herpesvirus 68 vBCL2 (M11), and statistical inference techniques, we show that regions of M11 transiently unfold and refold upon binding of the BH3D. Further, we show that this partial unfolding/refolding within M11 is mediated by a network of hydrophobic interactions, which includes residues that are 10 Å away from the BH3D binding cleft. We experimentally validate the role of these hydrophobic interactions by quantifying the impact of mutating these residues on binding to the Beclin1/BECN1 BH3D, demonstrating that these mutations adversely affect both protein stability and binding. To our knowledge, this is the first study detailing the binding-associated conformational changes and presence of long-range interactions within vBCL2s

    Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

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    The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

    On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

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    N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

    Seaweed resources off Tamil Nadu coast: Sector III. Valinokkam - Kilakkarai

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    Survey of seaweed resources in deep water was carried out in the area between Valinokkam and Kilakkarai during January 1989 and March,l990 respectively. In the survey from Valinokkam to Kilakkarai 33 species of marine algae were recorded of which 8 species belong to Chlorophyta, 8 to Phaeophyta and 17 to Rhodophyta. Only one species of seagrass Halophila ovalis was recorded. Among the 200 sq Icm area surveyed, vegetation occurred only in 27.5 sq.km with a total standing crop of 2962.5 tonnes (wet wt)

    Seaweed resources off Tamil nadu coast, Sector - IV Kilakkarai - Rameswaram island (Dhanushkodi

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    Survey of the deep water area from Kilakkarai (Appa Tivu to Rameswaram Island (Dhanushkodi) was undertaken from December 1990 to January 1991 in the IV Sector survey of Deep water Seaweed Resources off Tamil Nadu coast, which formed the last phase of the survey from Rameswaram to Kanyakumari carried out during 1986-91. An area of 417 .5 sq.km. was surveyed yielding a total biomass of 18,162.5 tons (wet) seaweeds. Out of 167 stations surveyed in 13 transects, vegetation occurred only in 12 stations. Of the 29 species of marine algae recorded 8 belonged to Chlorophyta, 8 to Phaeophyta, 12 to Rhodophyta, and I to Cyanophyta, One species of seagrass Cymodocea serrulata was also recorded. Twenty species were found in estimable quantities, of which the following 8 species were abundant: Halimeda macr%ba, Spatog/ossum asperum, Zonaria crenata, Sargassum ilicijolium, Amphiroa jragilissima, Hypnea muscijormis, Botryocladia /eplOpoda and Lyngbya majuscula with a biomass of 1325, 9775, 650, 1550, 1925,300,862.5 and 1012.5 tons (wet) respectively. The species of Hypnea and Sargassum could be exploited for the manufacture of phytochemicals
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