Adapter molecules

Horng T, Barton GM. Medzhitov R TIRAP an adapter molecule in the Toll signaling pathway. Nat Immunol 2001 2 835-841. 

As described in Chapters 35 and 38, the tRNA molecules serve as adapter molecules for the translation of... 

The cell must possess the machinery necessary to translate information accurately and efficiently from the nucleotide sequence of an mRNA into the sequence of amino acids of the corresponding specific protein. Clarification of our understanding of this process, which is termed translation, awaited deciphering of the genetic code. It was realized early that mRNA molecules themselves have no affinity for amino acids and, therefore, that the translation of the information in the mRNA nucleotide sequence into the amino acid sequence of a protein requires an intermediate adapter molecule. This adapter molecule must recognize a specific nucleotide sequence on the one hand as well as a specific amino acid on the other. With such an adapter molecule, the cell can direct a specific amino acid into the proper sequential position of a protein during its synthesis as dictated by the nucleotide sequence of the specific mRNA. In fact, the functional groups of the amino acids do not themselves actually come into contact with the mRNA template. 

SH2 and SH3 domains refer to src homology 2 and 3, a non-receptor tyrosine kinase where these domains were identified originally. They bind to phos-phorylated tyrosine and pro line rich epitopes, respectively, with specificities each in respect to the neighboring amino acids. Grb2 is an adapter molecule par excellence having both SH2 and SH3 domains (see also the respective article in this volume). 

Inasmuch as amino acids have no direct aflSnity for mRNA, an adapter molecule, which recognizes an amino add on one end and its corresponding codon on the other, is required for translation. This adapter molecule is tRNA. 

RNAs have a broader range of functions, and several classes are found in cells. Ribosomal RNAs (rRNAs) are components of ribosomes, the complexes that carry out the synthesis of proteins. Messenger RNAs (mRNAs) are intermediaries, carrying genetic information from one or a few genes to a ribosome, where the corresponding proteins can be synthesized. Transfer RNAs (tRNAs) are adapter molecules that faithfully translate the information in mRNA into a specific sequence of amino acids. In addition to these major classes there is a wide variety of RNAs with special functions, described in depth in Part HL... 

Messenger RNA is only one of several classes of cellular RNA. Transfer RNAs serve as adapter molecules in protein synthesis covalently linked to an amino acid at one end, they pair with the mRNA in such a way that amino acids are joined to a growing polypeptide in the correct sequence. Ribosomal RNAs are components of ribosomes. There is also a wide variety of special-function RNAs, including some (called ribozymes) that have enzymatic activity. All the RNAs are considered in detail in Chapter 26. The diverse and often complex functions of these RNAs reflect a diversity of structure much richer than that observed in DNA molecules. 

Other proteins interact with the receptors indirectly through adapter molecules which have no catalytic activity. Two well-known adapter proteins are Grb2476 and She.477478 The 25-kDa protein Grb2 consists entirely of recognition domains, one SH2 and two SH3 domains (Fig. 11-14). The larger She, which is found in all mammalian tissues, contains a 200-residue phosphotyrosyl-binding PH domain (Chapter 7) at the N terminus, a... 

In addition to structural roles, it is becoming increasingly apparent that a major function of IFs is to regulate the activities of cell metabolism, by serving as scaffolding for the dynamic regulation of associated proteins such as enzymes, signaling adapter molecules, stress proteins, cell death receptors, and even the endocytic machinery. 

Fig. 20.2. Simplified scheme describing the central dogma in molecular biology. DNA is replicated and passed from one generation to the next. For protein biosynthesis, DNA sequence is first transcribed into complementary messenger RNA (mRNA) sequence which, by means of the adapter molecule transfer RNA (tRNA), is translated into protein sequence. The translation follows the genetic code where a nucleotide triplet (e.g., AGC) codes for an amino acid (e.g., serine) [522]...

Alkaloids are apparently well-adapted molecules that can serve plants as potent defense chemicals which are used on their own or together with other mostly... 

The fidelity of protein synthesis requires the accurate recognition of three-base codons on messenger RNA. Recall that the genetic code relates each amino acid to a three-letter codon (Section 5.5.1). An amino acid cannot itself recognize a codon. Consequently, an amino acid is attached to a specific tRNA molecule that can recognize the codon by Watson-Crick base pairing. Transfer RNA serves as the adapter molecule that binds to a specific codon and brings with it an amino acid for incorporation into the polypeptide chain. 

Robert Holley first determined the base sequence of a tRNA molecule in 1965, as the culmination of 7 years of effort. Indeed, his study of yeast alanyl-tRNA provided the first complete sequence of any nucleic acid. This adapter molecule... 

Amino acids must be activated for translation to occur. Activation ensures that the correct amino acid will be recognized and fiiat there is sufficient energy for peptide bond formation. Activation is the covalent coupling of amino acids to specific adapter molecules. The adapter molecules are called transfer RNA (tRNA). There is atleast one tRNA for each of the 20 naturally occurring amino acids. The tRNA recognize the codons carried by the mRNA and position them to facilitate peptide bond formation. 

---