Protein dimerization

Figure Bl.17.11. Reconstructed density of an a,p-tiibulin protein dimer as obtained from electron crystallography (Nogales etal 1997). Note the appearance of the p-sheets ((a), marked B) and the a-helices ((b), marked H) in the density. In particular the right-handed a-helix H6 is very clear. Pictures by courtesy of E Nogales and Academic Press.

Fig. 8. De novo designed a-hehcal proteins. Dimers of the amphiphilic helix-forming peptide a B, GELEELLKKLKELLKG (see Table 1), in which the nature of the linker connecting the individual heflces plays a critical role in the stmcture of the final protein, (a) Using a Pro residue as the linker, ie, a B-Pro-a B, three molecules aggregated to form a trimeric coded-cod. (b) Using Pro-Arg-Arg as the linker, ie, a B-Pro-Aig-Arg-a, resulted in the...

Approximately 10 base pairs are required to make one turn in B-DNA. The centers of the palindromic sequences in the DNA-binding regions of the operator are also separated by about 10 base pairs (see Table 8.1). Thus if one of the recognition a helices binds to one of the palindromic DNA sequences, the second recognition a helix of the protein dimer is poised to bind to the second palindromic DNA sequence. 

The protein dimer binds so that the recognition a helices at opposite ends of the protein molecule are in the major groove of the DNA as predicted, where they interact with base pairs at the end of the DNA molecule. Since these binding sites are separated by one turn of the DNA helix, it follows that at the center of the DNA molecule the narrow groove faces the protein... 

Figure 16.20 The structure of the complex between a dimer of the coat protein of bacteriophage MS2 and the RNA fragment shown in Figure 16.19. One subunit of the coat protein dimer is green, the other is violet and the RNA fragment is orange. Bases that form sequence specific interactions with the protein are red. (Adapted from a diagram provided by L. Liijas.)...

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. 

Warwicker, J. (2000). Modeling a prion protein dimer Predictions for fibril formation. 

Janowski, R., Kozak, M., Jankowska, E., Grzonka, Z., Grubb, A., Abrahamson, M., and Jaskolski, M. (2001). Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping. Nat. Struct. Biol. 8, 316-320. 

JAKs and signal transducers and activators of transcription (STATs) are functionally analogous with IRS and PI3K. JAKs are physically associated with a cell surface receptor (e.g. for leptin, erythropoietin (EPO), growth factors or cytokines) STATs are free monomeric proteins within the cytosol but following phosphorylation by a JAK, individual proteins dimerize and then move into the nucleus of the cell where they control gene expression. 

Despite many biochemical similarities between linker and core histones the proteins of these two groups differ in architecture, evolutionary origin, and function. Each of the four core histones has a characteristic histone fold domain. The latter is an old and ubiquitous structural motif used in DNA compaction and protein dimerization [3]. Linker histones do not have a histone fold. The canonical... 

The following diagram, adapted from that first presented by Bennett et alC, describes a postulated pathway for evolution of a protein dimer from single-domain proteins. The scheme begins with the fusion of two singledomain polypeptides and proceeds through the evolution of interdomain contacts, and in the case of enzymes, development of an active site. These same interdomain contacts can also stabilize formation of a domain-swapped dimer which then undergoes further evolution into a present-day dimer. 

The use of the bifunctional PEG 2 resulted in the formation of a protein dimer linked by a PEG chain. It is worth stressing that this dimer construction was obtained in a single coupling step, even with a... 

Several lines of evidence demonstrate that the active unit of integrase is a multimer. It is clear, as an isolated protein in solution, that integrase forms dimers [6,10-12], and it has been shown by sedimentation equilibrium studies that Rous sarcoma virus (RS V) integrase exists in reversible equilibrium between monomeric, dimeric, and tetrameric forms [13]. Protein-protein cross-linking studies of HIV-1 [14] and RSV [15] integrases confirm the existence of protein dimers and tetramers in solution, and in vivo, the yeast GAL4 two-hybrid system has demonstrated that HIV-1 integrase can interact with itself [16]. 

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