Helicity conservation

The globin fold has been used to study evolutionary constraints for maintaining structure and function. Evolutionary divergence is primarily constrained by conservation of the hydrophobicity of buried residues. In contrast, neither conserved sequence nor size-compensatory mutations in the hydrophobic core are important. Proteins adapt to mutations in buried residues by small changes of overall structure that in the globins involve movements of entire helices relative to each other. 

Comparison of the amino acid sequences of the L and M subunits of the reaction centers from three different bacterial species shows that about 50% of all residues in those two subunits are conserved in all three species. In the transmembrane helices, sequence conservation varies. Residues that are buried and have contacts either with pigments or with other transmembrane helices are about 60% conserved. In contrast, residues that are fully exposed to the membrane lipids are only 16% conserved. Clearly, fewer restrictions... 

Figure 17.10 Construction of a two helix truncated Z domain, (a) Diagram of the three-helix bundle Z domain of protein A (blue) bound to the Fc fragment of IgG (green). The third helix stabilizes the two Fc-binding helices, (b) Three phage-display libraries of the truncated Z-domaln peptide were selected for binding to the Fc. First, four residues at the former helix 3 interface ("exoface") were sorted the consensus sequence from this library was used as the template for an "intrafece" library, in which residues between helices 1 and 2 were randomized. The most active sequence from this library was used as a template for five libraries in which residues on the Fc-binding face ("interface") were randomized. Colored residues were randomized blue residues were conserved as the wild-type amino acid while yellow residues reached a nonwild-type consensus, [(b) Adapted from A.C. Braisted and J.A. Wells,...

FIGURE 10.24 A helical wheel model of halorhodopsin. The amino acids facing the polar, hydrophilic core of the protein are shown. Of these 60 residues, 36 are conserved between halorhodopsin and bacteriorhodopsin. (Adapted from OesterMt, D., and Tittor, f, 1989. Treads ia Biochemical Scieaces 14 57—61.)... 

Note that below G = 1,200P , results may be too conservative. Gases in turbulent flow in circular helical coils ... 

Aquaporins. Figure 1 (a) The hour-glass model. The scheme depicts the six transmembrane helices (H1-H6), the connecting loops A-E, including the helical parts of loops B ((H)B) and E (E(H)), and the conserved NPA (Asn-Pro-Ala) motif of canonical aquaporins. (b) Structure of the conserved NPA motif region, flanked by the indicated helices, (c) Crystallographic structure of AQP1 tetramer. The four water pores in atetramer are indicated [1]. 

Sequence conservation is, in general, much weaker than structural conservation. There are proteins, which are clearly not related in sequence but are closely related in 3D-stmcture and fold, like heamoglobin and myoglobin, which have similar functions. In many proteins, fold elements like 4-helical bundles are repeated. Classifications of known structural folds of proteins are organized in the SCOP or CATH database see e.g., http //scop.mrc-lmb.cam.ac.uk/scop/. 

The universal antibiotic pactamycin targets a highly conserved region of 16S rRNA, contacting the tips of helices 23b and 24a in the central domain. Pactamycin folds up to mimic a RNA dinucleotide in that its... 

SNAPs is an acronym for soluble NSF attachment proteins. They were originally discovered as cofactors for NSF that mediate the membrane binding of NSF in in vitro transport assays. Several isoforms of SNAPs exist in mammalian cells. SNAPs are also highly conserved proteins. Crystallographic studies indicated that the proteins form a very stiff and twisted sheet that is formed by a series of antiparallel and tightly packed helices connected by short loops. 

SNARE motifs spontaneously assemble into SNARE complexes. These consist of a bundle of four intertwined a-helices that are connected by a total of 16 layers of mostly hydrophobic amino acid side chains. In the middle of the bundle, there is a highly conserved and polar 0-layer consisting of three glutamine and one arginine residue. These residues are among the most conserved in the SNARE superfamily and led to a classification of SNAREs into Q- and R-SNAREs, respectively. Different fusion steps require different sets of SNAREs but some SNAREs can participate in different complexes, and some fusion steps involve several SNARE complexes that appear to operate in parallel and independently. 

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