Headpieces

Figure S.7 The subunit structure of the neuraminidase headpiece (residues 84-469) from influenza virus is built up from six similar, consecutive motifs of four up-and-down antiparallel fi strands (Figure 5.6). Each such motif has been called a propeller blade and the whole subunit stmcture a six-blade propeller. The motifs are connected by loop regions from p strand 4 in one motif to p strand 1 in the next motif. The schematic diagram (a) is viewed down an approximate sixfold axis that relates the centers of the motifs. Four such six-blade propeller subunits are present in each complete neuraminidase molecule (see Figure 5.8). In the topological diagram (b) the yellow loop that connects the N-terminal P strand to the first P strand of motif 1 is not to scale. In the folded structure it is about the same length as the other loops that connect the motifs. (Adapted from J. Varghese et al.. Nature 303 35-40, 1983.)...

Boelens, R., et al. Complex of lac repressor headpiece with a 14 base-pair lac operator fragment studied by two-dimensional nuclear magnetic resonance. /. Mol. Biol. 193 213-216, 1987. 

Aufsatz, m. something set on attachment fixture head, headpiece neck top dome set (of china) essay, treatise, article, paper Dyeing) topping Calico) cover print, -farbe,/. Dyeing) topping color, -farbstoff, m. topping dye. -teil, m. supplement (to a periodical). 

A review is given of the application of Molecular Dynamics (MD) computer simulation to complex molecular systems. Three topics are treated in particular the computation of free energy from simulations, applied to the prediction of the binding constant of an inhibitor to the enzyme dihydrofolate reductase the use of MD simulations in structural refinements based on two-dimensional high-resolution nuclear magnetic resonance data, applied to the lac repressor headpiece the simulation of a hydrated lipid bilayer in atomic detail. The latter shows a rather diffuse structure of the hydrophilic head group layer with considerable local compensation of charge density. 

Combining structural and biochemical information, MacLennan and his colleagues [8,11,42,45,48,87] constructed a hypothetical model of the tertiary structure of Ca " -ATPase that has interesting mechanistic implications (Fig. 2). The structure was divided into three major parts, designated as the cytoplasmic headpiece, the stalk domain and the transmembrane domain each was assigned distinct functional... 

The headpiece contains five subdomains the N-terminal region (residues 1-40), the transduction or B domain (residues 131-238), the phosphorylation domain (residues 328-505), the nucleotide binding domain (residues 505-680) and the hinge domain (residues 681-738). The evidence supporting each of these assignments will be discussed in turn. 

FIGURE 5.30 Baron conditioner headpiece in use with a Desaga chamber 20 X 20 cm. 

REX-CPHMD simulations have also been applied to understand the mechanism of the formation of protein intermediate states. Recent solution NMR data revealed a sparsely populated intermediate in the villin headpiece domain, in which the N-terminal subdomain is largely random but the C-terminal subdomain adopts a nativelike fold [34], Interestingly, H41 in this intermediate state titrates at a pH value of... 

Another interesting application area of PHMD simulations is to investigate electrostatic interactions in the unfolded states of proteins. A traditional view that unfolded proteins adopt random conformational states that are devoid of electrostatic and hydrophobic interactions, are recently challenged by experimental data [20, 69], REX-CPHMD folding simulations of the 35 residue C-terminal subdomain of the villin headpiece domain revealed a significant deviation from the standard pKa values for several titratable residues. Additional simulations, in which a charged group is neutralized confirmed the existence of specific electrostatic interactions in the unfolded states (JK and CLB, manuscript in preparation). 

Khandogin J, Raleigh DP, Brooks CL III (2007) Folding intermediate in the villin headpiece domain arises from disruption of a N-terminal hydrogen-bonded network. J Am Chem Soc 129 3056-3057. 

We extrapolate from two simulations, the 10 ps simulation on bovine pancreatic trypsin inhibitor (BPTI) reported over twenty years ago [61] and the recent 1 gs simulation on the villin headpiece subdomain. [9] Each of these was a state-of-the-art simulation, using the best algorithms and the most powerful hardware available at the time. 

As in all computer applications for the past few decades, P has been growing exponentially with time. It is a straightforward calculation to show that in the 21 years between the BPTI simulation (t = KTns n 600) and the villin headpiece simulation (t = KT6 s n 12 000), P has been increasing by a factor of 10 every 3-4 years. A simple extrapolation would thus predict that a simulation covering the replication cyde of an intact E. coli with a volume of about 1 p3 (t 1000 s n=3x 1010) could be expected some time in the second half of the next century if computational power continued to grow exponentially at historical rates. 

Duan Y., Wang L. and Kouman P. A. The early stage of folding of villin headpiece sub-domain observed in a 200-nanosecond fully solvated molecular dynamics simulation. Proc. Natl. Acad. Sci., USA (1998) 95(17) 9897-9902. 

F. Culard, M. Schnarr, and J. C. Maurizot, Interaction between the lac operator and the lac repressor headpiece Fluorescence and circular dichroism studies, EMBO J. 1, 1405-1409 (1982). 

In addition to its influence on protein—protein interactions, phosphorylation also affects protein structure and activity. One case involves a protein termed dematin headpiece (DHP), an actin-binding protein found in a variety of tissues including heart, brain, skeletal muscle, kidney, and lung." DHP is known to interact with Ras-guanine nucleotide exchange factor (Ras-GRF2) and this interaction can modulate MARK pathways, which can link the cytoskeleton and signaling pathways." ... 

The cytoplasmic portion of Ca +-ATPase, sometimes called the cytosohc headpiece, contains three important domains. These are (1) the A (actuator or... 

De Mori, G.M.S., Colombo, G., Micheletti, C. Study of the villin headpiece folding dynamics by combining coarse-grained Monte Carlo evolution and all-atom molecular dynamics. Protein. Struct. Funct. Genet. 2005, 58, 459-71. 

Figure 28-3 (A) Ribbon view of the dimeric lac repressor bound to a natural operator and to the anti-inducer o-nitro-phenylfucoside (ONPF). The headpiece (residues 2-46) and the hinge helix (residues 50-58) form the DNA-binding domains. The core (residues 62-330), which is divided into N- and C-terminal subdomains, forms the binding site for ONPF. The C-terminal residues 334-360, which form a tetramerization domain, are absent from this MolScript drawing. Notice that the hinge helices bind to and widen the minor groove at the center of the operator. From Lewis et al.5a (B) Model of a 93-bp DNA loop corresponding to residues -82 to +11 of the lac operon (Fig. 28-2) bound to the tetrameric lac repressor. The active sites of the repressor are bound to the major operator O, and to the secondary operator 03. From Lewis et al.5...

Lee MR, Duan Y, Kollman PA (2000) Use of MM-PB/SA in estimating the free energies of proteins application to native, intermediates, and unfolded villin headpiece, Proteins, 39(4) 309-316... 

Figure 14.14. The 500-MHz 1H 2D NOESY spectrum of the lac repressor headpiece in H2O. (From ref. 4. Copyright 1985 by John Wiley Sons, Inc. Reprinted by permission.)...

This method of refinement was first applied, using the distance restraint form of Eq. [9], to the lac repressor headpiece using a model as the initial structure.9-83 It was later applied to a heptadecapeptide.84 Subsequent studies with model data showed that, with a carefully chosen simulation protocol, the method was capable of refining even poor starting structures.85 86... 

Restrained Molecular Dynamics Procedure for Protein Tertiary Structure Determination from NMR Data A lac Repressor Headpiece Structure Based on Information on /-Coupling and from Presence and Absence of NOEs. 

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