Beta Sandwich-Like Folds: Sequences, Contacts, Classification of Invariant Substructures and Beta Sandwich Protein Grammar.

This chapter addresses the following fundamental question: Do sequences of protein domains with sandwich architecture have common sequence characteristics even though they belong to different superfamilies and folds? The analysis was carried out in two stages: (1) determination of domain substructures shared by all sandwich proteins and (2) detection of common sequence characteristics within the substructures. Analysis of supersecondary structures in domains of proteins revealed two types of four-strand substructures that are common to sandwich proteins. At least one of these common substructures was found in proteins of 42 sandwich-like folds (per structural classification in the CATH database).

Overview of myelin, major myelin lipids, and myelin-associated proteins.

Myelin is a modified cell membrane that forms a multilayer sheath around the axon. It retains the main characteristics of biological membranes, such as lipid bilayer, but differs from them in several important respects. In this review, we focus on aspects of myelin composition that are peculiar to this structure and differentiate it from the more conventional cell membranes, with special attention to its constituent lipid components and several of the most common and important myelin proteins: myelin basic protein, proteolipid protein, and myelin protein zero.

Sequence Pattern for Supersecondary Structure of Sandwich-Like Proteins.

The goal is to define sequence characteristics of beta-sandwich proteins that are unique for the beta-sandwich supersecondary structure (SSS). Finding of the conserved residues that are critical for protein structure can often be accomplished with homology methods, but these methods are not always adequate as residues with similar structural role do not always occupy the same position as determined by sequence alignment. In this paper, we show how to identify residues that play the same structural role in the different proteins of the same SSS, even when these residue positions cannot be aligned with sequence alignment methods.

Amino acid distribution rules predict protein fold: protein grammar for beta-strand sandwich-like structures.

We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of "favorable" residues, that are mainly responsible for a given fold formation, and "unfavorable" residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation.

Amino acid distribution rules predict protein fold.

In the present article, we provide a brief overview of the main approaches to analysing the sequence-structure relationship of proteins and outline a novel method of structure prediction. The proposed method involves finding a set of rules that describes a correlation between the distribution of residues in a sequence and the essential structural characteristics of a protein structure. The residue distribution rules specify the 'favourable' residues that are required in certain positions of a polypeptide chain in order for it to assume a particular protein fold, and the 'unfavourable' residues incompatible with the given fold.

Finding of residues crucial for supersecondary structure formation.

This work evaluates the hypothesis that proteins with an identical supersecondary structure (SSS) share a unique set of residues--SSS-determining residues--even though they may belong to different protein families and have very low sequence similarities. This hypothesis was tested on two groups of sandwich-like proteins (SPs). Proteins in each group have an identical SSS, but their sequence similarity is below the "twilight zone.

A stringent test for hydrophobicity scales: two proteins with 88% sequence identity but different structure and function.

Protein-protein interactions (protein functionalities) are mediated by water, which compacts individual proteins and promotes close and temporarily stable large-area protein-protein interfaces. In their classic article, Kyte and Doolittle (KD) concluded that the "simplicity and graphic nature of hydrophobicity scales make them very useful tools for the evaluation of protein structures." In practice, however, attempts to develop hydrophobicity scales (for example, compatible with classical force fields (CFF) in calculating the energetics of protein folding) have encountered many difficulties.

New classification of supersecondary structures of sandwich-like proteins uncovers strict patterns of strand assemblage.

To describe the supersecondary structure (SSS) of beta sandwich-like proteins (SPs), we introduce a structural unit called the "strandon." A strandon is defined as a set of sequentially consecutive strands connected by hydrogen bonds in 3D structures. Representing beta-proteins as the assembly of strandons exposes the underlying similarities in their SSS and enables us to construct a novel classification scheme of SPs.

Protein--protein recognition: juxtaposition of domain and interface cores in immunoglobulins and other sandwich-like proteins.

Structural analysis of a non-redundant data set of 47 immunoglobulin (Ig) proteins was carried out using a combination of criteria: atom--atom contact compatibility, position occupancy rate, conservation of residue type and positional conservation in 3D space. Our analysis shows that roughly half of the interface positions between the light and heavy chains are specific to individual structures while the other half are conserved across the database. The tendency for conservation of a primary subset of positions holds true for the intra-domain faces as well.

Common features in structures and sequences of sandwich-like proteins.

The goal of this work is to define the structural and sequence features common to sandwich-like proteins (SPs), a group of very different proteins now comprising 69 superfamilies in 38 protein folds. Analysis of the arrangements of strands within main sandwich sheets revealed a rigorously defined constraint on the supersecondary substructure that holds true for 94% of known SP structures. The invariant substructure consists of two interlocked pairs of neighboring beta-strands.