Antiparallel relation

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.)...

In the first edition of this book this chapter was entitled "Antiparallel Beta Structures" but we have had to change this because an entirely unexpected structure, the p helix, was discovered in 1993. The p helix, which is not related to the numerous antiparallel p structures discussed so far, was first seen in the bacterial enzyme pectate lyase, the stmcture of which was determined by the group of Frances Jurnak at the University of California, Riverside. Subsequently several other protein structures have been found to contain p helices, including extracellular bacterial proteinases and the bacteriophage P22 tailspike protein. 

Most of the known antiparallel p structures, including the immunoglobulins and a number of different enzymes, have barrels that comprise at least one Greek key motif. An example is 7 crystallin, which has two consecutive Greek key motifs in each of two barrel domains. These four motifs are homologous in terms of both their three-dimensional structure and amino acid sequence and are thus evolutionarily related. 

Death domain (DD) superfamily consists of structurally related homotypic interaction motifs of approximately 90 amino acids. The motifs are organized in six antiparallel amphipathic a-helices, the so-called DD fold. The four members of the super family are the death domain (DD), the death effector domain (DED), the caspase activation and recruitment domain (CARD), and the Pyrin domain. All are important mediators for the assembly of caspase activating complexes. 

Fig. 8.—Packing arrangement of four symmetry-related 2-fold helices of mannan II (6). (a) Stereo view of two unit cells approximately normal to flic frc-plane. The two chains in the back (open bonds) and the two in the front (filled bonds) are linked successively by 6-0H-- 0-6 bonds. The front and back chains, both at left and right, are further connected by 0-2 -1V -0-2 bridges, (h) Projection of the unit cell along the c-axis the a-axis is down the page. This highlights the two sets of interchain hydrogen bonds between antiparallel chains, distinguished by filled and open bonds. The crossed circles are water molecules at special positions.

Two antiparallel helices, related by space group symmetry, are packed in an orthorhombic unit cell (Fig. 39b). There is substantial interdigitation between the helices so that side chains and main chains are linked by hydrogen bonds, such as 0-4E-0-4D (2,73 A) and 0-4D-0-3F (2.84 A) involving parallel and antiparallel strands, respectively. Plausible sites for sodium ions are near the... 

The most likely way for pardaxin molecules to insert across the membrane in an antiparallel manner is for them to form antiparallel aggregates on the membrane surface that then insert across the membrane. We developed a "raft"model (data not shown) that is similar to the channel model except that adjacent dimers are related to each other by a linear translation instead of a 60 rotation about a channel axis. All of the large hydrophobic side chains of the C-helices are on one side of the "raft" and all hydrophilic side chains are on the other side. We postulate that these "rafts" displace the lipid molecules on one side of the bilayer. When two or more "rafts" meet they can insert across the membrane to form a channel in a way that never exposes the hydrophilic side chains to the lipid alkyl chains. The conformational change from the "raft" to the channel structure primarily involves a pivoting motion about the "ridge" of side chains formed by Thr-17, Ala-21, Ala-25, and Ser-29. These small side chains present few steric barriers for the postulated conformational change. 

A rather common feature of subunit contacts is ft sheet hydrogenbonding between strands in opposite subunits. Theoretically the relationship could be a pure translation or a 2-fold screw axis with a one-residue translation (for a pair of parallel strands), but all the known cases of intersubunit /3 sheet bonding turn out to be between equivalent strands related by a local 2-fold axis. For hydrogen-bond formation, the 2-fold must be perpendicular to the /3 sheet, requiring the two equivalent strands to be antiparallel. Those may be the only two /3 strands (as in insulin, Fig. 63), or they may be part of antiparallel P sheets (as in prealbumin, Fig. 62), or the rest of the sheets may be parallel (as in alcohol dehydrogenase domain 1). 

Most of the antiparallel /3 domains have their sheets wrapped around into a cylinder, or barrel, shape. None of the antiparallel barrels has as symmetrical or as continuously hydrogen-bonded a cylindrical sheet as the singly wound parallel fi barrels of triosephos-phate isomerase and pyruvate kinase dl however, antiparallel barrels are very much more common. Because of gaps in the hydrogenbonding, some of these structures have been described as two /3 sheets facing each other (e.g., Schiffer et al., 1973 Blake et al., 1978 Harrison et al., 1978). Our reasons for treating them all as barrels are that the gap positions are sometimes different in domains that are probably related, and that the barrel description yields very much simpler and more unified topologies. 

The three-dimensional structural architecture of plant defensins is exemplified by the structure of Rs-AFP, ° which comprises an N-terminal /3-strand followed by an ct-helix and two /3-strands (/3a/3/3 configuration). The /3-strands form a triple-stranded antiparallel /3-sheet. The three-dimensional structure is stabilized by three disulfide bonds. In general, in plant defensins two disulfide bonds form between the ct-helix and the central /3-strand. A third disulfide bond stabilizes the structure by linking the /3-strand after the helix to the coiled part after the ct-helix. This motif is called the cysteine-stabilized a/3-motif (CSa/3)" and also occurs in toxins isolated from insects, spiders, and scorpions.The fourth disulfide bond links the C-terminal end of the peptide with the N-terminal /3-strand. Two plant defensins, PhDl and PhD2, feature a fifth disulfide bond and have been proposed to be the prototypes of a new subclass within plant defensins." As a result of these structural features the global structure of plant defensins is notably different from o //3-thionins, which is one of the reasons for the different nomenclature. The structures of plant defensins Rs-AFP ° and NaDf are shown in Figure 6, where they are compared to the thionin /3-purothionin and the structurally more related drosomycin and charybdotoxin. ... 

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