Conformations globular domain

Calmodulin (CaM) undergoes drastic conformational change when it binds Ca2+ and amphiphilic peptides such as mas to po ran and endorphin, which results in the modulation of many important biochemical reactions. The N-terminal and C-terminal of rigid structured globular domains are bridged with a long flexible peptide of a-helical structure. Each domain binds two Ca2+ ions to its hydrophobic sites. 

FIGURE 2 The structure of the globular domain of human PrP in monomeric (left) and dimeric (right) forms. The second subunit is gray to highlight the dramatic conformational change in the green a helix when the dimer is formed. 

Microorganisms typically express uptake systems specific for the siderophores that they synthesize as well as siderophores synthesized by other microbes, a strategy that allows them to compete for iron in an environment containing multiple microbial species. The structures of three OM receptors (FecA, FepA, and FhuA) are very similar to one another in that they are all -barrel proteins containing 22 antiparallel /3-strands that form a tube. The N-terminus forms a mobile globular domain that can occupy and occlude the chaimel formed in the center of the tube. When FhuA binds the ferrichrome near the outer surface of the central chaimel, major conformational changes occur both at the outer surface and on the periplasmic face of the receptor. The position of the globular cork domain then shifts to allow the bound siderophore to translocate across the membrane. 

The detailed structural information obtained from experiment for the globular domain of PrPc provides a starting point to perform MD simulations. One must realize, however, that uncertainties in the structure of PrP in aqueous solution still exist. Using protein NMR techniques, a set of conformational constraints is... 

Fig. 2 Conformational changes in the globular domain of PrP induced by acidic pH [59]. (a) Snapshots from a simulation at acidic pH, indicating the loss of hydrophobic contacts between the SI-HA loop and HC, followed by displacement of the N-terminal end of HA. (b) Ca traces of simulations at neutral, mildly acidic and strongly acidic pH from left to right. Structures of five simulations at each pH regime are shown for every 1 ns in the 25-50 ns time interval. The parts of HB and HC that remain stable (in agreement with experiment) are indicated by darker colors. In both panels, N-terminal residues 90-124 are omitted for clarity...

Fig. 4 Changes in conformation and flexibility caused by pathogenic mutations [126]. (a) Typical conformation and flexibility for WT PrP, T183A PrP and F198S PrP. Only the globular domain (res. 128-228) is shown. Flexibility is indicated by the thickness of the ribbon and the mutation site is indicated by a red sphere, (b) Early misfolding events in a simulation of VI801 PrP. First, an additional strand appears on the native sheet. Thereafter, hydrophobic contacts between HC and the SI-HA loop are lost and HA moves out to solvent. Mutation site is indicated by a sphere. For clarity, res. 90-112 are omitted...

Fig. 3. Stereo view of the all heavy-atom presentation of a single conformer of the globular domain in bPrP(121-230). Brown color is used for 20 amino side chains that form a hydrophobic core of the protein molecule (see text).

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