Bulletin of the American Physical Society
2008 APS March Meeting
Volume 53, Number 2
Monday–Friday, March 10–14, 2008; New Orleans, Louisiana
Session D17: Focus Session: Time-Resolved Structural Investigations on Protein Folding and Function |
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Sponsoring Units: DBP Chair: Aihua Xie, Oklahoma State University Room: Morial Convention Center 209 |
Monday, March 10, 2008 2:30PM - 3:06PM |
D17.00001: Folding dynamics of a family of beta-sheet proteins Invited Speaker: Fatty acid binding proteins (FABP) consist of ten anti-parallel beta strands and two small alpha helices. The beta strands are arranged into two nearly orthogonal five-strand beta sheets that surround the interior cavity, which binds unsaturated long-chain fatty acids. In the brain isoform (BFABP), these are very important for the development of the central nervous system and neuron differentiation. Furthermore, BFABP is implicated in the pathogenesis of a variety of human diseases including cancer and neuronal degenerative disorders. In this work, site-directed spin labeling combined with EPR techniques have been used to study the folding mechanism of BFABP. In the first series of studies, we labeled the two Cys residues at position 5 and 80 in the wild type protein with an EPR spin marker; in addition, two singly labeled mutants at positions 5 and 80 in the C80A and C5A mutants, respectively, were also produced and used as controls. The changes in the distances between the two residues were examined by a pulsed EPR method, DEER (Double Electron Electron Resonance), as a function of guanidinium hydrochloride concentration. The results were compared with those from CW EPR, circular dichroism and fluorescence measurements, which provide the information regarding sidechain mobility, secondary structure and tertiary structure, respectively. The results will be discussed in the context of the folding mechanism of the family of fatty acid binding proteins. [Preview Abstract] |
Monday, March 10, 2008 3:06PM - 3:42PM |
D17.00002: Ultrafast studies of flavins and flavoproteins Invited Speaker: Flavin molecule plays an essential role as a cofactor in flavoproteins with its rich redox states. We have systematically studied the excited-state dynamics of three different redox states (oxidized, semiquinone, and fully reduced) in bulk solvent and in some important proteins. A series of new results were obtained and a correlation of structure-redox-dynamics-function in proteins was observed. We use two important proteins, photolyase and flavodoxin, to show these significant findings. [Preview Abstract] |
Monday, March 10, 2008 3:42PM - 3:54PM |
D17.00003: Coupled folding and binding kinetics in the intrinsically disordered peptide IA$_{3}$ Ranjani Narayanan, Omjoy Ganesh, Arthur Edison, Stephen Hagen IA$_{3}$ is an intrinsically disordered 68 residue peptide and is an endogenous inhibitor of yeast proteinase A (YPrA). X-ray crystallography of the IA$_{3}\cdot $YPrA complex [Li et al, Nat. Struct. Biol. (7), 113-117 (2000)] indicates that the N-terminus of IA$_{3}$ adopts an alpha-helical fold when it is bound to the YPrA active site. We have used equilibrium circular dichroism and multi-wavelength, nanosecond time-resolved laser temperature-jump spectroscopy to study the coupled folding and binding interaction of IA$_{3}$ with YPrA. Our initial measurements of the rate of helix formation in free IA$_{3}$ indicate mono-exponential folding kinetics that extrapolate to k$_{F} \sim $ 10$^{5}$/s at room temperature in aqueous solutions. By comparing this rate to the kinetics we observe for IA$_{3}$ interacting with YPrA, we can assess possible mechanisms for the coupled folding and binding of IA$_{3}$. [Preview Abstract] |
Monday, March 10, 2008 3:54PM - 4:06PM |
D17.00004: Impact of Salt and Water on Protein Structural Dynamics Anu Thubagere, Lorand Kelemen, Beining Nie, Sandip Kaledhonkar, Aihua Xie Water is known as the lubricant of life. Without water, most proteins would lose their biological functions. Extensive studies have been carried out on how high concentration salts (dissolved in water) alter the stability and solubility of proteins. Such effects are thought to be mediated via salt-water interactions and water-protein interactions. This classic research field is known as the Hofmeister Series. We report the effects of Hofmeister Salts on the structural dynamics of proteins. Photoactive yellow protein (PYP), a bacterial blue light photoreceptor protein, is employed as a model system in this study. Time-resolved FTIR spectroscopic techniques allow us to probe the structural changes in proteins. Our data reveal that high concentration salt solutions alter the proton transfer pathway and suppress conformational changes in PYP upon photo-excitation. This study opens up a new dimension in the field of Hofmeister series. Further theoretical and experimental studies are needed in order to understand the dynamic properties of salt-water interactions and water-protein interactions. [Preview Abstract] |
Monday, March 10, 2008 4:06PM - 4:18PM |
D17.00005: Direct protein photoinduced conformational changes using porphyrins. Lorenzo Brancaleon, Ivan Silva, Nicholas Fernandez, Eric Johnson, Samuel Sansone Most proteins functions depend on the interaction with other ligands. These interactions depend on uniquely structured binding sites formed by the folding of the proteins. Ligands can often prompt intended as well as ``accidental'' protein structural changes. One can foresee that the ability to prompt and control post-translational protein folding could be a powerful tool to investigate protein folding mechanisms but also to inhibit certain proteins or induce new properties to proteins. One possible way to produce such structural disruption is the combination of light and photoactive ligands. This option has been investigated in recent years by exploiting photoisomerization and other properties of non-physiological dyes. We used an alternative approach which uses porphyrins as the ``triggers'' of structural changes. The advantage of porphyrins is that they can be found naturally in living cells. The photophysical properties of porphyrins can induce local as well as long range effects on the structure of the bound protein. Porphyrins are known to produce structural changes in porphyrin-specific proteins, however the novelty of our results is that we demonstrated that these dyes can also produce structural changes in non-porphyrin-specific globular proteins. We will present an overview of our research to-date in this field and its potential applications. [Preview Abstract] |
Monday, March 10, 2008 4:18PM - 4:30PM |
D17.00006: Computer simulations of the folding mechanism of the GCN4 Leucine zipper Yanxin Liu, Prem Chapagain, Jose Parra, Bernard Gerstman A modified three dimensional lattice model incorporating a Monte Carlo Metropolis Algorithm is used to investigate the dimerization of the GCN4 Leucine zipper. The model is validated with heat capacity calculations that are seen to match well with experiment measurements. The free energy landscape is investigated as a function of temperature. Evidence of multiple meta-stable states is found during the simulation. The possible folding and dimerization mechanism of the Leucine zipper will be discussed. [Preview Abstract] |
Monday, March 10, 2008 4:30PM - 4:42PM |
D17.00007: Describing protein folding through the evolution of spatial density Xianghong Qi, John J. Portman The capillarity-like structure of folding nuclei is directly characterized for a wide range of two state folding proteins within a variational model that includes ``neutral'' cooperativity. We find that on average the volume of the folded core depends on the number of monomers as $V_{\rm{f}} \sim N_{\rm{f}}^{0.3}$. The precise relation agrees with the packing of rigid objects that are typically twice the size of a monomer in the native state. Focusing on the growth of the folded core and the interface region, we identify three different growth modes: core and interface consolidation, core dominated consolidation, and balanced growth. We also show in detail how the density of the core and interface of critical nuclei determine the common qualitative characterization as either diffuse or polarized. Such analysis will aid interpretation of $\phi$-value distributions in terms of the spatial density or compactness of the critical nucleus which is much more difficult to probe experimentally than the degree of similarity to the native state. [Preview Abstract] |
Monday, March 10, 2008 4:42PM - 4:54PM |
D17.00008: The trigger sequence in the protein folding and dimerization of the Leucine zipper coiled-coil motif Prem Chapagain, Yanxin Liu, Bernard Gerstman The existence of a trigger sequence in the protein folding and dimerization of the Leucine zipper coiled-coil structure is attracting increased interest. Also of interest is the presence of multiple meta-stable states in the folding and unfolding process. Using a computer lattice model, we investigate the effect of the trigger sequence by changing the strength of the propensity of the amino acids in the trigger sequence to form alpha-helix secondary structure. The results show that the trigger sequence is necessary for folding and dimerization. The trigger sequence also creates a folding and dimerization process that includes multiple meta-stable states. [Preview Abstract] |
Monday, March 10, 2008 4:54PM - 5:06PM |
D17.00009: Correlation functions of flexible macromolecules Donald Jacobs, Dennis Livesay, Oleg Vorov We present an ab initio calculation of conformational entropy, radii of gyration, X-ray and neutron scattering form-factors, correlation functions, and other observables describing proteins, polypeptides, nucleic acids, related macromolecules and artificial polymers [1]. The analytic form of the method minimizes computational costs and reveals relations between observables. We apply these methods to study thermodynamics of protein unfolding. The presented results agree with the results from experiment and simulation [2]. \newline [1] O.K.Vorov, A.Y.Istomin, D.R.Livesay, D.J.Jacobs, subm. to Phys.Rev.Lett., 2007. [2] O.K.Vorov, D.R.Livesay, D.J.Jacobs, to be subm. to Proc. Natl. Acad. Sci., 2007, in preparation. [Preview Abstract] |
Monday, March 10, 2008 5:06PM - 5:18PM |
D17.00010: ABSTRACT WITHDRAWN |
Monday, March 10, 2008 5:18PM - 5:30PM |
D17.00011: Photocycle of a single photoactive yellow protein molecule studied by surface-enhanced Raman scattering Kaan Kalkan, Kushagra Singhal, Wouter Hoff, Aihua Xie We have demonstrated the detection of single molecules of photoactive yellow protein (PYP), by employing our novel surface-enhanced Raman scattering (SERS) active substrates. The Raman spectra reveal both ``receptor'' (G) and ``signaling'' (B) states of PYP at the single molecule level (at 514 nm excitation). The single molecule spectra are observed in terms of sudden appearance of discernable Raman peaks, each indicative of a PYP molecule finding a hot spot. The SERS spectra also exhibit various peaks, which are not normally Raman-active. Although the PYP has a long-lived signaling state (i.e., $\sim$0.3 s), the Raman peaks identifying this state are found to be dramatically narrow at the single molecule level for signal integration times of 0.25-0.5 s. In several instances, we observed subsequent change of the spectrum from B to G state. Although, the PYP is not chemisorbed on the metal nanoparticles, its short-term pysisorption is anticipated to allow for the capture of its photocycle at the single molecule level. In addition to narrower and better resolved peaks, the single molecule spectra also show variation in relative peak intensities. In particular, the C-C stretching and C-H bending modes of the aromatic ring of the chromophore inversely correlate at the single molecule level, while their intensities are comparable in the ensemble-average spectrum. [Preview Abstract] |
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