Encoded protein

The sequence space of proteins is extremely dense. The number of possible protein sequences is 20. It is clear that even by the fastest combinatorial procedure only a very small fraction of such sequences could have been synthesized. Of course, not all of these sequences will encode protein stmctures which for functional purjDoses are constrained to have certain characteristics. A natural question that arises is how do viable protein stmctures emerge from the vast sea of sequence space The two physical features of folded stmctures are (l)in general native proteins are compact but not maximally so. (2) The dense interior of proteins is largely made up of hydrophobic residues and the hydrophilic residues are better accommodated on the surface. These characteristics give the folded stmctures a lower free energy in comparison to all other confonnations. 

Tomarev, S. I., et al. (1993). Abundant mRNAs in the squid light organ encode proteins with a high similarity to mammalian peroxidases. Gene 132 219-226. 

BID is a member oftheBcl-2 gene family, which encode proteins that function either to promote apoptosis or to inhibit apoptosis as in the proteins derived from Bcl-2. These proteins can exist as monomers or they can dimerize. For example, if two promoting Bcl-2 family proteins dimerize then apoptosis will be greatly enhanced. Conversely, if dimerization of an inhibitory and promotor protein occurs, then the effects are cancelled out. The Bcl-2 family of proteins are localized to the outer mitochondrial or outer nuclear membranes. 

Pseudogenes are nonfunctional relatives of known genes that have lost their ability to encode proteins. 

The nuclear-encoded proteins are inserted into both inner and outer mitochondrial membranes, the intermembrane space, and the matrix and there are several different mechanisms involved. As mentioned above there is no apparent requirement for a presequence on proteins which insert specifically into the mitochondrial outer membrane. For proteins destined for the inner mitochondrial membrane, a stop-transfer mechanism is proposed. Thus some information in the peptide must stop the complete transfer of the protein into the mitochondrial matrix, enabling the protein to remain in the inner mitochondrial membrane. For some proteins in the intermembrane space (for example the Rieske iron-sulphur protein associated with the outer face of complex III), a particularly complicated import pathway... 

In this context, it should be noted that the specific antiviral activity of ganciclovir against HSV (which is more potent than that of acyclovir) can be fully explained by the compound being specifically recognized as substrate by the HSV-encoded TK. For CMV, however, which does not encode a virus-specified TK, the activity of ganciclovir depends on the phosphorylation by a vims-encoded protein kinase, which... 

Recombinant DNA technology can also be used to create modified proteins that are readily purified by affinity chromatography. The gene of interest is Unked to an oligonucleotide sequence that encodes a carboxyl or amino terminal extension to the encoded protein. The... 

Rephcation errors, even with a very efficient repair system, lead to the accumulation of mutations. A human has 10 nucleated cells each with 3 X 10 base pairs of DNA. If about 10 cell divisions occur in a lifetime and 10 mutations per base pair per cell generation escape repair, there may evenmaUy be as many as one mutation per 10 bp in the genome. Formnately, most of these will probably occur in DNA that does not encode proteins or will not affect the function of encoded proteins and so are of no consequence. In addition, spontaneous and chemically induced damage to DNA must be repaired. 

THE NUCLEOTIDE SEQUENCE OF AN mRNA MOLECULE CONSISTS OF A SERIES OF CODONS THAT SPECIFY THE AMINO ACID SEQUENCE OF THE ENCODED PROTEIN... 

There is a normal variation of DNA sequence just as is true of more obvious aspects of human structute. Variations of DNA sequence, polymorphisms, occur approximately once in evety 500 nucleotides, or about 10 times per genome. There are without doubt deletions and insertions of DNA as well as single-base substitutions. In healthy people, these alterations obviously occur in noncoding regions of DNA or at sites that cause no change in function of the encoded protein. This heritable polymorphism of DNA structure can be associated with certain diseases within a large kindred and can be used to search for the specific gene involved, as is illustrated below. It can also be used in a variety of applications in forensic medicine. 

Table 46-9. Some disorders due to mutations in genes encoding proteins involved in intracellular membrane transport. ...

Various Disorders Result From Mutations in Genes Encoding Proteins Involved in Intracellular Transport... 

The greatest surprise provided by the results to date has been the apparently low number of genes encoding proteins, estimated to lie between 30,000 and 40,000. The higher number could increase as new data are obtained. This number is approximately twice that found in the roundworm (19,099) and three times that of the fruit... 

An alternative approach is to synthesize an artificial gene in the test-tube starting with the appropriate deoxyribonucleotides. This approach, which demands that the entire amino acid sequence be known, has been used to clone genes encoding proteins 200 amino acids long. 

Tremblay MJ, Fortin JF, Cantin R. The acquisition of host-encoded proteins by nascent HIV-1. Immunol Today 1998 19(8) 346-351. 

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