P-Sheet structures

Open p-sheet structures have a variety of topologies... 

We have described a general relationship between structure and function for the a/p-barrel structures. They all have the active site at the same position with respect to their common structure in spite of having different functions as well as different amino acid sequences. We can now ask if similar relationships also occur for the open a/p-sheet structures in spite of their much greater variation in structure. Can the position of the active sites be predicted from the structures of many open-sheet a/p proteins ... 

In almost every one of the more than 100 different known a/p structures 1 of this class the active site is at the carboxy edge of the p sheet. Functional residues are provided by the loop regions that connect the carboxy end of the strands with the amino end of the a helices. In this one respect a fun-I damental similarity therefore exists between the a/p-barrel structures and the I open a/p-sheet structures. 

Edison, A.S. Propagation of an error p-sheet structures. Trends Biochem. Sci. 15 216-217, 1990. 

These results indicate that is it possible to change the fold of a protein by changing a restricted set of residues. They also confirm the validity of the rules for stability of helical folds that have been obtained by analysis of experimentally determined protein structures. One obvious impliction of this work is that it might be possible, by just changing a few residues in Janus, to design a mutant that flip-flops between a helical and p sheet structures. Such a polypeptide would be a very interesting model system for prions and other amyloid proteins. 

Fig. 2 (a) Antiparallel and (b) parallel P-sheet structures of two peptide chains connected by hydrogen bonds... 

Like the other pectate lyases, PelZ folding appears to be mainly based on p-sheet structures. Moreover, PelZ possesses only one cysteine residue and thus can not present any intramolecular disulfide bond The folding process of this protein may be different from that of... 

Jeong and coworkers have reported peptide-based thermo-gelling systems using PEG-b-polyAla as an injectable cellular scaffold [315]. The polymer aqueous solution undergoes sol-gel transition as temperature increases. The fraction of the p-sheet structure of the poly Ala dictated the population and thickness of fibrous nanostructure in the hydrogel, which affected the proliferation and protein... 

To this amylase structure, CGTase adds 2 other subdomains (D E), which are antiparallel P-sheets at the C-terminal end of the protein. The structure of domain D is similar to immimoglobulin topology. Tlie frmctional role of these domains is not known. However, proximity of domain E (an antiparallel P-sheet structure) to the proposed catalytic site, suggests a role in substrate binding and conformation. 

Figure 2-2. Structures of a-helix and P-sheet Dashed lines indicate hydrogen bonds that stabilize these types of secondary structure. The hydrogen bonds of the a-helix are intrastrand, ie, formed between the backbone carbonyl oxygen and the amide hydrogen four amino acids up the helix. R groups represent the side chains in the a-helix. Side chains that would project above and below the plane of the page in the P-sheet structures have been omitted for clarity. Hydrogen bonds stabilizing the p-sheet are interstrand, ie, formed between groups on neighboring strands.

For an octapeptide sequence taken from the C-terminal residues of the Alzheimer s Ap-peptide Lansbury et al. identified a large intensity enhancement for 13C-labeled modes that was sequence-dependent and assessed as largely due to interstrand dipole-coupling.1207,2351 Mendelsohn et al. found a similar effect by double labeling on alternate sites a peptide that formed a P-sheet-like structure in methanol.12501 Subsequent theoretical modeling showed this latter intensity enhancement to be a function of forming extended, flat, anti-parallel P-sheet structures,12511 and the overall effect to be highly position sensitive.12451... 

The physical and chemical properties of the AChR have been elucidated. Optical rotatory dispersion measurements indicate that the receptor consists of about 34% helix and 28-30% P-sheet structure—a high proportion of ordered secondary structure. Some carbohydrates are part of the molecule. The DNA encoding the receptor has been cloned and sequenced, revealing the complete amino acid sequence of the subunits. 

P-sheet structures as DNA-binding motifs are found in pro- and eucaryotic DNA-binding proteins. As an example, the structure of the MetJ repressor from E. coli is shown in Fig. 1.9. The DNA is contacted in the major groove by the protruding P-strands. 

The eukaryotic transcription factor NFxB also binds DNA via P-sheet structure (Fig. 1.10). Noteworthy is the enshrouding of the DNA by the P-sheets of NFxB. The recognition of the DNA elements is also achieved by interaction with the major groove of the DNA. 

Fig. 5.3. Structure of the OmpF porin of E. coli. The porin is a bacterial membrane protein with P-sheet structures as transmembrane elements. The structure of a monomer of the OmpF porin is shown. In total, 16 P-bands are configured in the form of a cylinder and form the waUs of a pore through which selective passage of ions takes place. LI—L8 are long loops, Tl,2,3 and T7,8 are short bends (T turn) that fink the P-sheets. According to Cowan et al. (1992), with per-...

At present, it is generally assumed that transmembrane receptors span the cell membrane as a-helices. However, it is not known how often other structural elements occur in the transmembrane domains of receptors. Tlius, the presence of P-sheet structures, particularly in the case of receptors with complex structures, cannot be excluded (Hucho et al., 1994). 

The catalytic domain of protein kinase A has a two lobe structure, composed of a smaller lobe with a large portion of P-sheet structures and a larger lobe that is mostly a-helical. All Ser/Thr- and Tyr-specific protein kinases structurally characterized to date show a similar domain structure. 

The structure of the complex indicates a specific interaction between P-sheet structures of Raf kinase and structural elements of RaplA protein belonging to the switch I region, which are thus part of the RaplA protein effector domain. Since RaplA protein has a very similar structure to Ras protein, it is assumed that Ras protein also interacts with Raf kinase via its switch I region. 

The exact mechanism by which the depolarization leads to movement of the voltage sensor is not known. A simple model is under discussion, in which the S4 helix turns outwards by one helix turn during opening and thus leads to outward transport of 1—2 charges. A more complex model assumes a conformational change of the S4 helix in which the outward transport of charges is associated with conversion of a a-helix into a P-sheet structure. 

---