Protein Dynamics in Cytochrome b6f Explored by Spectral Hole Burning

Proteins perform vital functions in the living organisms. They need to fold into their final tertiary structure in order to function properly. However, knowing the static tertiary structure of a protein is not enough to understand how it functions since proteins are not rigid bodies. The fact that the proteins go through structural fluctuations has to be taken into account in studying these complex biomolecules. Optical techniques, such as spectral hole burning, can be used in studying the dynamics of proteins. However, most proteins must be doped with dye molecules as probes since most of the proteins do not absorb light in visible region. Pigment-protein complexes involved in photosynthesis are good model systems for studying protein dynamics since the pigment molecules are embedded in these proteins naturally. Understanding the dynamics of proteins involved in photosynthesis and the way they function is important also from the perspective of photosynthesis and renewable energy research. The focus of this seminar is on the low-temperature dynamics and the barrier distributions on the energy landscape of Cytochrome b6f Protein Complex. Qualitatively, the distributions of barriers between protein sub-states involved in the light-induced conformational changes (i.e. - Non-Photochemical Hole Burning (NPHB)) are close to glass-like, and not to Gaussian. Spectral dynamics of Cytochrome b6f manifesting in NPHB experiments appears to be independent of the deuteration of the buffer/glycerol glassy matrix containing the protein. Proton tunneling in the water/glycerol solvent environment can be excluded as the origin of the observed NPHB and recovery dynamics. Entities involved in the light-induced conformational changes are characterized by md^2 = 2.7-3.6 . 10^-46 kg.m^2. Evidence is presented for excitation energy transfer between chlorophyll molecules of the adjacent monomers. The magnitude of the dipole-dipole coupling deduced from the FLN spectra is in good agreement with the structural data, indicating that explored protein was intact

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization

Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

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Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.</p

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.</p

Conformational changes in pigment-protein complexes at low temperatures - spectral memory and a possibility of cooperative effects

40 Pags.- 9 Figs. The definitive version is available at: http://pubs.acs.org/journal/jpcbfkWe employed non-photochemical hole burning (NPHB) and fluorescence line narrowing (FLN) spectroscopies to explore protein energy landscapes and energy transfer processes in dimeric cytochrome b6f, containing one chlorophyll molecule per protein monomer. The parameters of the energy landscape barrier distributions quantitatively agree with those reported for other pigment-protein complexes involved in photosynthesis. Qualitatively, the distributions of barriers between protein sub-states involved in the light-induced conformational changes (i.e. - NPHB) are close to glass-like ~1/√V (V is the barrier height), and not to Gaussian. There is a high degree of correlation between the heights of the barriers in the ground and excited states in individual pigment-protein systems, as well as nearly perfect spectral memory. Both NPHB and hole recovery are due to phonon-assisted tunneling associated with the increase of the energy of a scattered phonon. As the latter is unlikely for simultaneously both the hole burning and hole recovery, proteins must exhibit a NPHB mechanism involving diffusion of the free volume towards the pigment. Entities involved in the light-induced conformational changes are characterized by md2 value of about 1.0.10-46 kg.m2. Thus, these entities are protons or, alternatively, small groups of atoms experiencing sub-Å shifts. However, explaining all spectral hole burning and recovery data simultaneously, employing just one barrier distribution, requires a drastic decrease in the attempt frequency to about 100 MHz. This decrease may occur due to cooperative effects. Evidence is presented for excitation energy transfer between the chlorophyll molecules of the adjacent monomers. The magnitude of the dipole-dipole coupling deduced from the delta-FLN spectra is in good agreement with the structural data, indicating that explored protein was intact.Concordia researchers express gratitude to NSERC, CFI and Concordia University. We would also like to acknowledge the financial support by the MINECO (Grant AGL2011-23574) to R. P.Peer reviewe

Spatially heterogeneous structure-function coupling in haemodynamic and electromagnetic brain networks

The relationship between structural and functional connectivity in the brain is a key question in connectomics. Here we quantify patterns of structure-function coupling across the neocortex, by comparing structural connectivity estimated using diffusion MRI with functional connectivity estimated using both neurophysiological (MEG-based) and haemodynamic (fMRI-based) recordings. We find that structure-function coupling is heterogeneous across brain regions and frequency bands. The link between structural and functional connectivity is generally stronger in multiple MEG frequency bands compared to resting state fMRI. Structure-function coupling is greater in slower and intermediate frequency bands compared to faster frequency bands. We also find that structure-function coupling systematically follows the archetypal sensorimotor-association hierarchy, as well as patterns of laminar differentiation, peaking in granular layer IV. Finally, structure-function coupling is better explained using structure-informed inter-regional communication metrics than using structural connectivity alone. Collectively, these results place neurophysiological and haemodynamic structure-function relationships in a common frame of reference and provide a starting point for a multi-modal understanding of structure-function coupling in the brain

Neurophysiological signatures of cortical micro-architecture

Abstract Systematic spatial variation in micro-architecture is observed across the cortex. These micro-architectural gradients are reflected in neural activity, which can be captured by neurophysiological time-series. How spontaneous neurophysiological dynamics are organized across the cortex and how they arise from heterogeneous cortical micro-architecture remains unknown. Here we extensively profile regional neurophysiological dynamics across the human brain by estimating over 6800 time-series features from the resting state magnetoencephalography (MEG) signal. We then map regional time-series profiles to a comprehensive multi-modal, multi-scale atlas of cortical micro-architecture, including microstructure, metabolism, neurotransmitter receptors, cell types and laminar differentiation. We find that the dominant axis of neurophysiological dynamics reflects characteristics of power spectrum density and linear correlation structure of the signal, emphasizing the importance of conventional features of electromagnetic dynamics while identifying additional informative features that have traditionally received less attention. Moreover, spatial variation in neurophysiological dynamics is co-localized with multiple micro-architectural features, including gene expression gradients, intracortical myelin, neurotransmitter receptors and transporters, and oxygen and glucose metabolism. Collectively, this work opens new avenues for studying the anatomical basis of neural activity

Probing nergy landscapes of cytochrome b6f with spectral hole burning: Effects of deuterated solvent and detergent

36 Pags.- 9 Figs. The definitive version is available at: http://pubs.acs.org/journal/jpcbfkIn non-photochemical spectral hole burning (NPHB) and spectral hole recovery experiments, cytochrome b6f protein exhibits behavior that is almost independent of the deuteration of the buffer/glycerol glassy matrix containing the protein, apart from some differences in heat dissipation. On the other hand, strong dependence of the hole burning properties on sample preparation procedures was observed and attributed to a large increase of the electron–phonon coupling and shortening of the excited-state lifetime occurring when n-dodecyl β-d-maltoside (DM) is used as a detergent instead of n-octyl β-d-glucopyranoside (OGP). The data was analyzed assuming that the tunneling parameter distribution or barrier distribution probed by NPHB and encoded into the spectral holes contains contributions from two nonidentical components with accidentally degenerate excited state λ-distributions. Both components likely reflect protein dynamics, although with some small probability one of them (with larger md2) may still represent the dynamics involving specifically the −OH groups of the water/glycerol solvent. Single proton tunneling in the water/glycerol solvent environment or in the protein can be safely excluded as the origin of observed NPHB and hole recovery dynamics. The intensity dependence of the hole growth kinetics in deuterated samples likely reflects differences in heat dissipation between protonated and deuterated samples. These differences are most probably due to the higher interface thermal resistivity between (still protonated) protein and deuterated water/glycerol outside environment.Work at Concordia was supported by NSERC, CFI and Concordia University. R.P. and M.A.L. acknowledge support by the Ministry of Economy and Competiveness of Spain (Grant No. AGL2014-55300-R) and Aragon Government (Grant E33).Peer reviewe