Hexamer Model Research Articles

An all-atom model of the pore-like structure of hexameric VP40 from Ebola: Structural insights into the monomer–hexamer transition

The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) to a resolution of ∼30 Å. In this paper, we present the refinement of the EM reconstruction of truncated hexameric VP40 to ∼20 Å and the construction of an all-atom model (residues 44–212) using the EM model at ∼20 Å and the X-ray structure of monomeric VP40 as templates. The hexamer model suggests that the monomer–hexamer transition involves a conformational change in the N-terminal domain that is not evident during octamerization and therefore, may provide the basis for elucidating the biological function of VP40.

Theoretical study of the secondary structures of unionized Poly(γ-D-glutamic acid)

Poly(γ-D-glutamic acid), 1, the only natural γ-peptides, have many important biological functions. The secondary structures of a hexamer model of unionized γDPGA, 3, have been studied by a quantum mechanical method (B3LYP/6-31G*), including the solvent effect using the SCIPCM model. Frequency calculations were carried out using the HF/6-31G* method. Calculations indicate that a right-handed 19-helix is the most stable secondary structure. The calculated electronic circular dichroism spectrum of the right-handed 19-helix agrees with the experimental spectrum quite well, which further supports the above prediction. A right-handed 14-helical structure is also found to be quite stable in the gas phase.

Helix Formation and Folding in γ‐Peptides and Their Vinylogues

AbstractA complete overview of all possible periodic structures with characteristic H‐bonding patterns is provided for oligomers composed of γ‐amino acids (γ‐peptides) and their vinylogues by a systematic conformational search on hexamer model compounds employing ab initio MO theory at various levels of approximation (HF/6‐31G*, DFT/B3LYP/6‐31G*, SCRF/HF/6‐31G*, PCM//HF/6‐31G*). A wide variety of structures with definite backbone conformations and H‐bonds formed in forward and backward directions along the sequence was found in this class of foldamers. All formally conceivable H‐bonded pseudocycles between 7‐ and 24‐membered rings are predicted in the periodic hexamer structures, which are mostly helices. The backbone elongation in comparison to α‐ and β‐peptides allows several possibilities to realize identical H‐bonding patterns. In good agreement with experimental data, helical structures with 14‐ and 9‐membered pseudocycles are most stable. It is shown that the introduction of an (E)‐double bond into the backbone of the γ‐amino acid constituents, which leads to vinylogous γ‐amino acids, supports the folding into helices with larger H‐bonded pseudocycles in the resulting vinylogous γ‐peptides. Due to the considerable potential for secondary‐structure formation, γ‐peptides and their vinylogues might be useful tools in peptide and protein design and even in material sciences.

Crystal Structure of ClpA, an Hsp100 Chaperone and Regulator of ClpAP Protease

Escherichia coli ClpA, an Hsp100/Clp chaperone and an integral component of the ATP-dependent ClpAP protease, participates in regulatory protein degradation and the dissolution and degradation of protein aggregates. The crystal structure of the ClpA subunit reveals an N-terminal domain with pseudo-twofold symmetry and two AAA(+) modules (D1 and D2) each consisting of a large and a small sub-domain with ADP bound in the sub-domain junction. The N-terminal domain interacts with the D1 domain in a manner similar to adaptor-binding domains of other AAA(+) proteins. D1 and D2 are connected head-to-tail consistent with a cooperative and vectorial translocation of protein substrates. In a planar hexamer model of ClpA, built by assembling ClpA D1 and D2 into homohexameric rings of known structures of AAA(+) modules, the differences in D1-D1 and D2-D2 interfaces correlate with their respective contributions to hexamer stability and ATPase activity.

A comparison between Anderko's model with composition-dependent physical interaction parameters and SRK-based hexamer model for HFC and HF systems

A new composition-dependent mixing rule in physical contribution term of AEOS by Anderko [A. Anderko, Phase equilibria in aqueous systems from an equation of state based on the chemical approach. Fluid Phase Equilibria, 1991, 65, 89.] was introduced to predict the phase behavior for HFC-134a+HF and HFC-32+HF binary systems. The approach developed in this work gives better results for systems containing strongly associating compounds in the vapor phase such as hydrogen fluoride than the SRK-based hexamer model developed by Twu et al. [C.H. Twu, J.E. Coon, J.R. Cunningham, A new cubic equation of state for hydrogen fluoride, Fluid Phase Equilibria 1993, 86, 47.] with fewer binary adjustable parameters. The equation of Peng and Robinson [D.Y. Peng, D.B. Robinson, A new two-constant equation of state. Ind. Eng. Chem. Fundam., 1976, 15, 59.] is used to describe the physical interactions. The van der Waals mixing rule was replaced by composition-dependent mixing rules to improve the predictability of this model. This study shows more accurate results for VLE phase behavior for HFC and HF systems than the SRK-based hexamer model or any other activity coefficient-based hexamer models developed so far.

Phage phi29 protein p6 is in a monomer-dimer equilibrium that shifts to higher association states at the millimolar concentrations found in vivo.

Protein p6 from Bacillus subtilis phage phi29 (Mr = 11 800) binds in vitro to DNA forming a large nucleoprotein complex in which the DNA wraps a multimeric protein core. The high intracellular abundance of protein p6 together with its ability to bind the whole phi29 DNA in vitro strongly suggests that it plays a role in viral genome organization. We have determined by sedimentation equilibrium analysis that protein p6 (1-100 microM range), in the absence of DNA, is in a monomer-dimer equilibrium, with an association constant (K2) of approximately 2 x 10(5) M-1. The intracellular concentration of protein p6 (approximately 1 mM) was estimated measuring the number of copies per cell (7 x 10(5)) and the cell volume (1 x 10(-15) L). At concentrations around 1 mM, protein p6 associates into oligomers. This self-association behavior is compatible with a dimer-hexamer model (K2,6 = 3.2 x 10(8) M-2) or with an isodesmic association of the dimer (K = 950 M-1), because the apparent weight-average molecular mass (Mw,a) does not reach saturation at the highest protein concentrations. The sedimentation coefficients of protein p6 monomer and dimer were 1.4 and 2.0, respectively, compatible with translational frictional ratios (f/fo) of 1.15 and 1.30, which slightly deviate from the hydrodynamics of a rigid globular protein. Taking together these results and considering the structure of the nucleoprotein complex, we speculate that the observed oligomers of protein p6 could mimic a scaffold on which DNA folds to form the nucleoprotein complex in vivo.

1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling.

Interleukin 6 (IL-6) has many biological activities in vivo, and deregulation has been implicated in many disease processes. IL-6, a 185 amino acid polypeptide was refolded, purified and crystallized. The crystals diffracted to beyond 1.9 A and the structure was solved using single isomorphous replacement. The X-ray structure of IL-6 is composed of a four helix bundle linked by loops and an additional mini-helix. 157 out of 185 residues are well defined in the final structure, with 18 N-terminal and 8 A-B loop amino acids displaying no interpretable electron density. The three-dimensional structure has been used to construct a model of IL-6 interacting with the IL-6 receptor (alpha-chain) and gp130 (beta-chain) that gives new insight into the process of molecular recognition and signaling. Based on this model, we predict a fourth binding site on IL-6, a low affinity IL-6-IL-6 interaction, which may be necessary for the sequential assembly of a functional hexameric IL-6 receptor complex.

Monte Carlo Simulations of the Chemical Potential and Free Energy for Trimer and Hexamer Rings

Abstract The chemical potential of a trimer and hexamer model ring system was determined by computer simulation over a range of temperatures and densities. Such ring molecules are important as model aromatic and naphthenic hydrocarbons. Thermodynamic integration of the pressure along a reversible path, Widom's ghost particle insertion method and Kirkwood's charging parameter method were used over a molecular density range of 0.05 to 0.30. Data were obtained by Monte Carlo simulation of a 96 molecule system that was modelled with a Lennard-Jones 6-12 truncated potential. The original insertion method, which does not take into account the orientation of the molecule when it is inserted, gives results for the chemical potential which deviate from that obtained using the thermodynamic pressure integration. At high density or temperature the deviation is significant. We have modified the Widom insertion technique to account for this short range orientation and find good agreement between this technique and the...

La glutamate déshydrogénase de la luzerne : aspects cytologiques, structuraux et évolutifs

The 28 isozymes of the glutamate dehydrogenase (GDH) from Medicago sativa L. pollen result from the random association of three different subunits that form a hexamer enzyme. We show in this paper that: (i) all the isozymes have a mitochondrial localization; (ii) the only mutant that we found in the species (among about 350 individuals) can also be explained by adjusting the distribution of band intensities to a multinomial distribution. The principles of this method are detailed; (iii) the zymograms obtained from other organs accord with the hexamer model of the enzyme; (iv) this mitochondrial GDH is probably homologous to all the mitochondrial GDH, whether they come from plants or animals.

Ab initio MO-SCF calculation on a model of anomalous water

Ab initio calculations are carried out on the planar hexamer model of anomalous water using a variety of basis sets. The results are compared to results of similar calculations on free water and water in the ice I-like puckered ring configurations.