Apolar residues

Menashi et al.153) could confirm the results of Privalov and Tiktopulo152 and inter-prete the described effects as follows In the case of native tropocollagen, the pyrrolidine residues are probably directed away from the fibrillar axis and are mostly coated by water which is structured in the immediate neighbourhood to the pyrrolidine residues. During the denaturation these pyrrolidine residues form hydrophobic bonds with each other or with other apolar residues within the same chain (endothermic interaction) while the structure of water breaks down (increase of entropy). 

Upon alignment of 25 endo- and exo-polygalacturonases taken from the swiss.prot. database only one histidine appeared to be conserved throughout. The conserved histidine at position 223 in PGII was changed into alanine, a small apolar residue. 

I-Solenoid repeats usually have several x or x x sequence patterns that correspond to the /1-strands (here, denotes an apolar residue, and x is mostly polar but can be any residue except pro line). The middle -position in x x usually has a bulky apolar residue, while -residues in positions close to turns are often alanine, glycine, serine, or threonine. These positions are also occupied by asparagine residues that stack to form H-bonded ladders inside the /1-solenoid. The strand-associated x and x x patterns are interrupted by regions enriched in polar residues and glycine (Hennetin et al., 2006). These are regions of turns and loops. The long loops frequently contain proline residues. In several /1-solenoids, the alternation of apolar and polar residues that is typical for /1-strands is not well observed and outside positions are occupied by apolar residues. 

Finally, L-type /2-solenoids have an unusual inverted arch (Fig. 12). Stacking of these arches makes a groove which forms the center of the binding site for polysaccharides or pectins (Jenkins and Pickersgill, 2001). In contradistinction to the other arches, the arc residues of inverted arches are interior-facing and are apolar, while residues in the -conformation which bound the arc, face the solvent and are mostly polar (Fig. 12). These arcs have ab conformations. Frequently the first arc residue is small, glycine or alanine, and the second position is occupied by a bulky apolar residue. 

Fig. 14. Structural prediction and modeling of a fragment of FHA from B. pertussis containing Rl-repeats. (A) Successive stages in the modeling. From top to bottom identification of the consensus sequence repeat, generation of 2D template of the coil, and the modeled 3D structure. In the consensus sequence, letters indicate residues that are conserved at the level of >60% identity, x is any residue and filled circles represent bulky nonpolar residues. Apolar residues are in red glycine in green. In the 2D template, open circles denote any (but mainly polar) residues, while filled circles denote conserved, mainly nonpolar, residues. Circles inside the coil contour indicate side chains located inside the structure and circles outside the contour denote side chains facing the solvent. Arrows indicate /(-strands. (B) A fragment of the crystal structure of FHA (Clantin et al, 2004) (on the top, in green color) and the 3D model (bottom, in brown).

The van der Waals model of monomeric insulin (1) once again shows the wedge-shaped tertiary structure formed by the two chains together. In the second model (3, bottom), the side chains of polar amino acids are shown in blue, while apolar residues are yellow or pink. This model emphasizes the importance of the hydrophobic effect for protein folding (see p. 74). In insulin as well, most hydrophobic side chains are located on the inside of the molecule, while the hydrophilic residues are located on the surface. Apparently in contradiction to this rule, several apolar side chains (pink) are found on the surface. However, all of these residues are involved in hydrophobic interactions that stabilize the dimeric and hexameric forms of insulin. 

Fn adsorbed on hydrophobic silica, however, fluoresces at 326, suggesting a slight denaturation of the molecule. Fn interactions with the hydrophobic surface may involve some of the apolar residues in the protein interior, suggesting a partial denaturation. Clearly, studies on surfaces of a range of charge, polarity, and apolar character would be of interest. 

Type C repeats are very common in proteins. They are quantal in length, but the repeats themselves do not contain residues that are conserved absolutely in any position. However, several positions within the repeats are strongly conserved in character. A classic example of a Type C repeat is that given by the heptad substructure in a-fibrous proteins. This has the form (a—b-c—d—e—f—g)n with the a and d positions generally occupied by apolar residues, and the e and g positions by charged or hydrophilic residues. The heptad is characteristic of an Q-helical conformation (Cohen and Parry, 1986, 1990 Lupas, 1996), but comparison of any two sequences with a heptad substructure generally reveals only about 15—20% identity. The motif also implies that several Q-helices will aggregate to form a multistranded left-handed coiled-coil rope to shield the apolar stripes on the surface of the Q-helices from the aqueous environment. 

Tropomyosin is a two-stranded, o-helical coiled-coil molecule that aggregates head-to-tail with others to form long filamentous ropes. These lie in each of the two long period grooves of the actin microfilaments where, in vertebrate skeletal muscle, they play an important part in the Ca2+-mediated regulation of actin via troponin (a tropomyosin-associated protein). An important feature of tropomyosin is its 39.2-residue period— that is also quasi-halved (19.6 residues)—in the linear distribution of the acidic residues and, to a lesser extent, the apolar residues (McLachlan and Stewart, 1976 Parry, 1975). The number of residues in tropomyosin (284 residues), and the head-to-tail overlap (nine residues) that allows axial... 

Fig. 9. The conformation adopted by a leucine-rich repeat (LRR) is that of a /9-strand followed by an o-helix. In porcine ribonuclease inhibitor, a /9-strand (residues 2-8) is connected to an o-helix (residues 14—27) by a connecting loop (residues 9-13). A horseshoe-shaped structure is formed and is exemplified in the crystal structure of ribonuclease inhibitor (PDB 1A4Y Kobe and Deisenhofer, 1993). This has an inner concave surface formed by curved /9-sheets and an outer convex surface formed by oh el ices. The leucines and other large apolar residues form the hydrophobic core of the structure.

Segment 1A is defined in large part by its underlying heptad repeat, which has the form (a-b-c-d-e-f-g) n, where positions a and d are largely occupied by apolar residues. Such a motif is characteristic of an a-helical conformation that aggregates with others to form a multistranded coiled-coil rope. In the case of IF molecules, there are two strands only, which are aligned parallel to one another and in axial register (see, for example,... 

Analyses of the tropomyosin sequence have shown long-range periodicities of certain surface acidic and apolar residues that are likely to be recognition sites for actin. These features are discussed below in relation to their role in regulation (see Turning on the Thin Filament section). 

Fig. 4. Schematic illustration of how hydrophobic periodicity can influence secondary structure formation. In this illustration, the closed circles symbolize apolar residues and open circles symbolize polar residues. In dilute, aqueous solution, the peptides lack a single defined conformation. However, in the presence of an apolar-water interface, they adopt a secondary structure that maximizes the interactions of the apolar groups with the apolar medium and the polar groups with water. Taken from DeGrado and Lear (1985).

Fig. 7. (A) Aligned, partial sequences of a number of calmodulin-binding peptides. The boxes indicate residues that are generally occupied by apolar residues. Reported dissociation constants for interaction with calmodulin are given on the right. LK2, A mode peptide VIP, vasoactive intestinal peptide GIP, gastric inhibitory peptide. (B) The mean hydropho-bicities for the residues at a given position were plotted versus their position in the aligned sequence. The horizontal bar indicates the period of an a helix. From Cox et al. (1985).

The conformation of most proteins is such that in aqueous solutions the more polar hydrophilic amino acids, i.e. lysine, serine, threonine, aspartic and glutamic acids are exposed to the aqueous environment and the apolar residues are buried in the interior of the molecule by virtue of hydrophobic interactions. 

Generally, the introduction of apolar molecules (such as hydrocarbons or noble gases), or apolar residues in otherwise polar molecules (such as alkyl side chains in biopolymers) into water leads to a reduction of the degrees of freedom (spatial, orientational, dynamic) of the neighbouring water molecules. This effect is called the hydro-phobic effect or hydrophobic hydration [176], Hydrophobic means water-fearing . It should be noted that the interaction between hydrophobic molecules and water molecules is actually attractive because of the dispersion interactions. However, the water/ water interaction is much more attractive. Water molecules simply love themselves too much to let some other compounds get in the way [26b] Therefore, from the point of view of the water molecules, the term hydrophobic is rather a misnomer it would be better to refer to water as being lipophobic . 

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