Protein assemblies, structural similarities

Simons KT, Kooperberg C, Huang E, Baker D. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J Mol Biol 1997 268 209-25. 

The distinguishing feature of CS H2A is a nine amino acid extension on its C-terminus. The possibility that CS H2A is the sea urchin H2A.X has been raised on the basis of its structure and its similarity to a large H2A stored in Xenopus eggs that was identified as H2A.X [127] this Xenopus protein has been identified as H2.X on the basis of its position in two dimensional gels and its peptide map [129], but its sequence has not been determined. The C-terminal sequence of CS H2A (SMEY) resembles the SQ(ED)(ILFY) consensus of H2AX. The Xenopus and sea urchin proteins also show similar phosphorylation patterns during chromatin assembly [128,129]. Additional studies will be required to determine the relationship, if any, between CS H2A and H2A.X. 

Early studies on amino acid/peptide derived amphiphiles revealed that their ability to assemble into various architectures was controlled by surprisingly small structural differences. The hydrophobic residues in the peptide amphiphiles have shown to shield themselves from water and to self-assemble in a manner similar to the protein folding. The similarity of their self-assembling properties to those of proteins, initiated numerous studies for the determination of the relationship between the structure of an individual amino acid or a specific peptide sequence and the resulting architecture. 

The successful synthesis of the biohybrid members of the family of amphiphiles, the giant amphiphiles, has also attracted the spotlight of fundamental sciences. The incorporation of biological molecules (proteins and enzymes) in to the amphiphilic structure mimics the self-assembly seen in Nature by amphiphilic proteins. Though enzymes and proteins have been extensively funtionalized in the past, the realization that they can express assembling properties similar to that of their molecular and polymeric counterparts offers new methods for the construction of functional biomimetic assemblages. The future for amphiphiles appears to be unlimited. 

It is well known that well-ordered (3-chitin (a polysaccharide) associated with a less ordered protein in the (3-sheet conformation is the main component of nacreous organic matrix in shell. The amino acid sequence of such proteins is very similar to those of silk fibroins. Indeed, the amino acid sequence of a major protein from the nacreous shell layer of the pearl oyster resembles that of spidroin (Sudo et al., 1997 Weiner and Traub, 1980). The question of whether silk-like proteins play an important role in shell formation is raised. When Falini et al. (1996) did the experiment with the proteins from the shell, they assembled a substrate in vitro that contained (3-chitin and natural silk fibroin and concluded that the silk fibroin may influence ion diffusion or the accessibility to the chi tin surface or both. Furthermore, cryo-TEM study of the structure of the Atrina shell nacreous organic matrix without dehydration... 

In terms of viral assembly and structure the baculovirus system has been used with tremendous success and some representative examples are discussed in more detail below. Generally speaking, the expressed viral protein (s) can be expected to assemble into particles that are structurally similar if not identical to their native counterparts. This has been shown specifically in the case of the nodavirus Flock House virus, where X-ray analysis of native virions and VLPs showed no differences in the structure of the protein capsid (V. Reddy and J. E. Johnson [The Scripps Research Institute, La JoUa, CA], unpublished data). Similarly, structural investigations at lower resolution, using cryoelectron microscopy and three-dimensional image reconstruction, have confirmed the identity of native and synthetic virions in many other cases. This feature combined with the large amounts that can be obtained has permitted structural analysis of many viruses for which only limited amounts of native virions were available. 

A protein with a similar dumbell shape and structure is troponin C of skeletal muscles. Troponin C binds to a complex of proteins that assemble on the thin actin filaments of muscle fibers and control con-trachon in response to changes in the calcium ion con-centrahon (Chapter 19). Other proteins that contain EF-hand mohfs and are therefore responsive to Ca + include spectrin of cell membranes, clathrin light chains from coated vesicles, the extracellular osteonectin of bones and teeth, ° and a birch pollen anhgen. 2 Another group of 17 or more small SlOO EF-hand proteins play a variety of other roles. One of these, which has a high affinity for Zn +, has been named psoriasin because of its 5-fold or greater... 

In the protein world structural conservatism and diversity are combined on two different levels conservatism in the more macroscopic, that is, the structural level and diversity on the microscopic level, that is, the individual amino acid sequence. The fold defines the scaffold of the protein, that is, the 3D structure of the amino acid backbone, as well as the shape and size of the active site and the spatial orientation of the catalytic residues. The individual amino acid side chains forming the active site and its catalytic residues determine the molecular interactions between the protein and the ligand. The same fold can be assembled by amino acid sequences with only as little as a few percent sequence similarity. Thus both, fold and sequence, determine together the binding properties of any protein and enable the vast number of specific functions to be carried out by a limited number of fold types. ... 

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