Heterodimer structure

Zhao X, Wang XZ, Jiang XK, Chen YQ, Li ZT, Chen GJ. Hydrazide-based quadruply hydrogen-bonded heterodimers, structure, assembling selectivity, and supramolecular substitution. J Am Chem Soc 2003 125 15128-15139. 

The Chi fl /P700 ratio has taken the zigzag (2/1/2/1) path over the past fifteen years. I understand that a series of reports are being put out by these workers to detail the experimental results for this new development. Based on the new results, P700 may be considered as a heterodimer consisting of one Chi d and one Chi a molecule each, although, admittedly, definitive evidence for the heterodimer structure remains to be established. 

Of the five cofactors that are participants in the generation of tubulin heterodimers, structural information is thus far available for only one,... 

Zhang, J., Chalmers, M.J., Stayrook, K.R., et al. (2010) Hydrogen/deuteiium exchange reveals distinct agonist/partial agonist receptor dynamics within vitamin D receptor/retinoid X receptor heterodimer. Structure, 18 (10), 1332-1341. 

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

How is the binding specificity of the heterodimer achieved compared with the specificity of Mat a2 alone The crystal structure rules out the simple model that the contacts made between the Mat a2 homeodomain and DNA are altered as a result of heterodimerization. The contacts between the Mat o2 homeodomain and DNA in the heterodimer complex are virtually indistinguishable from those seen in the structure of the Mat o2 monomer bound to DNA. However, there are at least two significant factors that may account for the increased specificity of the heterodimer. First, the Mat al homeodomain makes significant contacts with the DNA, and the heterodimeric complex will therefore bind more tightly to sites that provide the contacts required by both partners. Second, site-directed mutagenesis experiments have shown that the protein-protein interactions involving the... 

Li, T, et al. Crystal structure of the MATal/MATa2 home-odomain heterodimer bound to DNA. Science 270 262-269, 1995. 

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

Helix-loop-helix (b/HLH) transcription factors are either heterodimers or homodimers with basic a-helical DNA-binding regions that lie across the major groove, rather than along it, and these helices extend into the four-helix bundle that forms the dimerization region. A modification of the b/HLH structure is seen in some transcription factors (b/HLH/zip) in which the four-helix bundle extends into a classic leucine zipper. 

Figure 13.13 (a) Schematic diagram of the Gpy heterodimer from transducln. The view Is along the central tunnel. The seven four-stranded p sheets that form the seven blades of the propeller-llke structure are labeled SI to S7. The strands are colored to highlight the seven WD sequence repeats. The N-termlnal a helices of the p and y chains form a colled coll. 

Wang, J., et al. Atomic structure of an ap T-cell receptor (TCR) heterodimer in complex with an anti-TCR Fab fragment derived from a mitogenic antibody. EMBO J. 17 10-26, 1988. 

Farnesyl transferase from rat cells is a heterodimer consisting of a 48 kD u-snbnnit and a 46 kD /3-snbnnit. In the structure shown here, helices 2 to 15 of the u-snbnnit are folded into seven short coiled coils that together form a crescent-shaped envelope partially surrounding the /3-snbnnit. Twelve helices of the /3-snl> nnit form a novel barrel motif that creates the active site of the enzyme. Farnesyl transferase inhibitors, one of which is shown here, are potent suppressors of tumor growth in mice, but their value in humans has not been established. 

A helix-loop-helix motif is a DNA-binding motif, related to the leucine-zipper. A helix-loop-helix motif consists of a short a helix, connected by a loop to a second, longer a helix. The loop is flexible and allows one helix to fold back and pack against the other. The helix-loop-helix structure binds not only DNA but also the helix-loop-helix motif of a second helix-loop-helix protein forming either a homodimer or a heterodimer. 

These nuclear receptors have several common structural features (Figure 43-12). All have a centrally located DNA-binding domain (DBD) that allows the receptor to bind with high affinity to a response element. The DBD contains two zinc finger binding motifs (see Figure 39-14) that direct binding either as homodimers, as heterodimers (usually with a retinoid X... 

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