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Highly structured and double-stranded (ds) RNAs are adaptable and potent biochemical entities. They interact with dsRNA-binding proteins (RBPs), the great majority of which contain a sequence called the dsRNA-binding motif (dsRBM). This approximately 70-amino-acid sequence motif forms a tertiary structure that interacts with dsRNA, with partially duplexed RNA and, in some cases, with RNA-DNA hybrids, generally without obvious RNA sequence specificity. At least nine families of functionally diverse proteins contain one or more dsRBMs. The motif also participates in complex formation through protein-protein interactions.

Protein sequencing evolved as part of studies in protein structure and function. A biochemist who made a significant contribution in the study of protein sequencing was Fred Sanger of the Biochemistry Dept in Cambridge University, UK. His end-group determination method was used as a groundwork for other sequencing techniques. The practice of protein sequencing provided an important breakthrough in the field of molecular genetics.

Our knowledge of the large family of proteins that contain the WD repeat continues to accumulate. The WD-repeat proteins are found in all eukaryotes and are implicated in a wide variety of crucial functions. The solution of the three-dimensional structure of one WD-repeat protein and the assumption that the structure will be common to all members of this family has allowed subfamilies of WD-repeat proteins to be defined on the basis of probable surface similarity. Proteins that have very similar surfaces are likely to have common binding partners and similar functions.

Hsc70s in the yeast endoplasmic reticulum (ER) and mitochondria interact with membrane-associated components of the translocation machinery and are required for post-translational protein import. Although it has been proposed that the mitochondrial and ER machines function similarly, a variety of experiments suggest that BiP, the ER hsc70, might play a more elaborate role.

The ability of a polypeptide to fold into a unique, functional, three-dimensional structure in vivo is dependent upon its amino acid sequence and the function of molecular chaperone proteins and enzymes that catalyse folding. Intense study of the physical chemistry and cell biology of folding have greatly aided our understanding of the mechanisms normally employed. Evidence is accumulating that many disease-causing mutations and modifications exert their effects by altering protein folding. Here we discuss the pathobiology of these processes.

Convergence as a phenomenon in molecular evolution is an issue that confuses many discussions. Often the problem is that not enough care is taken to state exactly what kind of convergence one has in mind. Functional and mechanistic convergence are both common, and some structural convergence has probably occurred, but a convincing case for genuine sequence convergence has yet to be made.

The amino acid sequences of enzymes like alcohol dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase are strongly conserved across all phyla. We suggest that the amino acid conservation of such enzymes might be a result of the fact that they function as part of a multi-enzyme complex. The specific interactions between the proteins involved would hinder evolutionary change of their surfaces.

Two unique motifs in the phosphatidylinositol (PI)-kinase superfamily are described. Called FAT and FATC, they probably fold together in a conformation that ensures proper function of the kinase.

The amino acid sequences of the polyglandular autoimmune syndrome protein, AIRE-1, and its additional domains were analyzed. It was believed that mutations of cloned AIRE-1 induced autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) although AIRE-1 has a significant function in gene expression. It was revealed that residue sequences of the proteins contain a SAND domain composed of Sp100, AIRE-1, NucP41/75 and DEAF-1 suppressin. The SAND domain implied that SAND proteins are DNA-binding transcription factors.

The bromodomain is a conserved sequence of 60-110 amino acids that exhibits a degree of homology with helicases and DNA-dependent adenosine triphosphatases. Bromodomains are located in variable regions within individual proteins such as in the middle of an amino acid sequence, the amino terminus or the carboxyl terminus of a specific protein. Bromodomain proteins were classified into six groups based on functional and amino acid sequence similarities.

Mass spectrometry-based proteomic methodologies can be used to annotate both nucleotide and protein sequence databases. Because such data have to be derived from proteins, they can be used to identify coding regions of the genome as well as provide the complete primary sequence of proteins and their expression patterns and post-translational modifications.

The database searches using SRm proteins yielded a PWI motif within the N-terminal domain of SRm 160 or at the C-terminus of the proteins from protozoans and Caenorhabditis elegans. It was suggested that the motif plays a significant role in pre-mRNA splicing as a result of its presence in two splicing factors. Also, it was indicated that the motif might have evolved as an important factor involved in the assembly of splicing complexes in higher eukaryotes, exemplified by the RS domains contained in some metazoan spliceosomal proteins.

The N-terminal portion of the Escherichia coli protein GutQ features a sugar isomerase (SIS) domain found in prokaryotic, archaebacterial and eukaryotic proteins. The SIS domain is vital factor in phosphosugar isomerization. This domain characteristic is also present in the KpsF E. coli protein and a hypothetical protein. GutQ also has two C-terminal cystathionine beta-synthase domains.

The R3H motif is a protein domain that binds single-stranded nucleic acids and is found in a diverse range of organisms. It is located at the N-terminus, C-terminus or in the center of a protein sequence. It contains an invariant arginine residue and a highly conserved histidine residue that are separated by three residues. It also exhibits a conserved pattern of hydrophobic residues, prolines and glycines.

The caspase recruitment domain (CARD) refers to the homologous RAIDD/ICH-1 amino terminal domain which mediates the recruitment of caspases to receptors during apoptotic signalling. The CARD was detected in the amino-terminal propeptide of ICH-1, Ced-3, interleukin-1beta-converting enzymes and Mch6. Furthermore, proteins such as cIAP1 and c-IAP2 contain CARD in their carboxy-terminal RING-finger and tumor-necrosis factor-binding BIR-repeats.

The tumor necrosis factor receptor-associated factors (TRAFs) domain regions are similar to the regions meprin metaloproteases. The conserved regions of both TRAF and meprins are characterized by a sequence of eight TRAF and eight meprin subunits. The presence of a subset of highly conserved amino acids is recognized as the meprin- and TRAF-homology (MATH) domain. The TRAF MATH domain is composed of protein-protein and TRAF-TRAF interactions that suggest a similar configuration for meprin MATH-domains.

Research has shown similarities between single continuous protein or DNA sequences. Evolutionary and structure-function relationships have been suggested by similar protein or DNA sequences. However, there have been cases when two discontinuous sequences are homologous to a continuous sequence having a sequential order of fragments. The case of a clearly homologous gene having an inverted sequential order is presented.

The cyclization of 2,3-oxidosgualene to lanosterol or cycloartenol is an important step in steroid biosynthesis. However, research has shown that pentacyclic hopanoids can be synthesize with the use of a large number of prokaryotes. Data from several research libraries also shows that the best homologous sequences are those that have the closest similarity to the protein sequence motifs of squalene and oxidosqualene.

Guanosine pentaphosphate phosphohydrolase (GPPA) and exopolyphosphatase (PPX) contain the conserved structure often found in the ATP-binding domain of the Hsp 70/actin/sugar kinase superfamily. This is according to a recent computer analysis of the two enzymes' amino acid sequences, which were compared with other amino acid sequence databases. Moderate similarities between the two enzymes and the product of the yeast gene RTG2 were obtained. RTG2 plays an important role in the regulation of inter-organelle communication.

Comparisons were made of the amino acid sequence of human hormone-sensitive lipase (HSL) and the lipases of the eubacteria Bacillus, Streptomyces, Moraxella and Escherichia. Similarities were found in the region bounded by identical catalytic site motifs. HSL and lipase 2 of Moraxella were found to be similarly cold-adaptive, retaining activities at temperatures colder than 4 degrees Celsius.

An SRC homology 2 (SH2) domain was located in the protein product of the SPT6 gene in the yeast Saccharomyces cerevisiae. SH2 domains are known to be present in proteins that act in growth regulation processes, binding the phosphorylated tyrosine residues of growth regulator proteins. SPT6 is a nuclear protein that may act as a transcription regulator. SH2 domains are likely to exist in the amino acid sequences of protists and plants.

A comparative study of the structures and ATP-binding properties of exopolyphosphate (Ppx) phosphatase and guanosine pentaphosphate (pppGpp) revealed that these two enzymes are homologous and that they belong to the same family of polyphosphates. This family includes sugar kinase, actin and prokaryotic cell proteins. Ppx and pppGpp are both synthesized in Escherechia coli. They have the same catalytic properties but different physiological functions in the bactreial cell.

A new type of Kunitz domain within the carboxy-terminal domain of NOGGIN is investigated. The Kunitz-type proteolytic enzyme inhibitor occurs in different situations and functions. Several important differences exist between NOGGIN and other Kunitz domains despite the unlikely possibility that the carboxy-terminal region of NOGGIN follows a Kunitz fold. The large differences suggests that NOGGIN may undergo binding under a different receptor molecule class, although the role of the aminoterminal domain remains unclear.

Proto-oncogene ret (c-Ret) exhibits similarities with cadherins based on similar repetitions in its primary structures and the position and sequence of the Ca2+ binding sites of the transmembrane protein. A search on the amino acid sequences of other proteins failed to identify similar findings. This identical feature suggests the possible role of c-Ret in a Ca2+-dependent binding to another c-Ret that induces tyrosine kinase activity and leads to cell to cell recognition events.

A new zinc-finger motif with the structure CX2CX9-27CXHX2CX6-17CX2C, where X is any amino acid, has been identified in a newly-discovered family of nuclear proteins. Apart from this motif, called the RING finger, several proteins in this family contain an associated B box motif and a coiled-coil domain. The B box and the coiled-coil domain in proteins such as T18 and PML may play an important role in the growth and differentiation of cells.

A system for analyzing protein sequences is described by its inventor. It can sequence samples containing complex mixtures of proteins even if they are present in very low concentrations. It can be completely automated and does not involve gel electrophoresis.

A consensus amino acid sequence has been identified as a probable nuclear targeting sequence. The sequence consists of a cluster of basic amino acids separated from another cluster by any 10 amino acids with three of the first five amino acids being basic. While eukaryotic DNA conserves this consensus sequence to a large extent, proteins involved in DNA repair in yeast and human cells do not show the consensus sequence.