Homodimer

Peng X, Wilson T E and Alivisatos A P 1997 Synthesis and isolation of a homodimer of oadmium selenide nanoorystals Angew. Chem. Int Ed. Engl. 36 145... 

Figure 10.19 Heterodimerization of leucine zipper proteins can alter their DNA-binding specificity. Leucine zipper homodimers bind to symmetric DNA sequences, as shown In the left-hand and center drawings. These two proteins recognize different DNA sequences, as indicated by the red and blue regions in the DNA. The two different monomers can combine to form a heterodimer that recognizes a hybrid DNA sequence, composed of one red and one blue region.

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... 

In contrast to Myc, Max can form homodimers that bind tightly to DNA. These homodimers recognize the same consensus sequence as members of the b/HLH family, 5 -CANNTG-3. The three-dimensional structure of the b/HLH/zip domain of Max complexed with a DNA fragment containing the sequence 5 -CACGTG-3 has been determined by the group of Stephen... 

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. 

The terms polypeptide and protein are used interchangeably in discussing single polypeptide chains. The term protein broadly defines molecules composed of one or more polypeptide chains. Proteins having only one polypeptide chain are monomeric proteins. Proteins composed of more than one polypeptide chain are multimeric proteins. Multimeric proteins may contain only one kind of polypeptide, in which case they are homomultimeric, or they may be composed of several different kinds of polypeptide chains, in which instance they are heteromultimeric. Greek letters and subscripts are used to denote the polypeptide composition of multimeric proteins. Thus, an ag type protein is a dimer of identical polypeptide subunits, or a homodimer. Hemoglobin (Table 5.1) consists of four polypeptides of two different kinds it is an hetero-multimer. 

The HIV-l protease is a remarkable viral imitation of mammalian aspartic proteases It is a dimer of identical subunits that mimics the two-lobed monomeric structure of pepsin and other aspartic proteases. The HIV-l protease subunits are 99-residue polypeptides that are homologous with the individual domains of the monomeric proteases. Structures determined by X-ray diffraction studies reveal that the active site of HIV-l protease is formed at the interface of the homodimer and consists of two aspartate residues, designated Asp and Asp one contributed by each subunit (Figure 16.29). In the homodimer, the active site is covered by two identical flaps, one from each subunit, in contrast to the monomeric aspartic proteases, which possess only a single active-site flap. 

FIGURE 17.19 ff-Acdnin exists as a homodimer of andparallel snbnnits, illnstrated here in terms of their primary strnctnre. The N-ter-miiral, actin-binding domain and the C-termi-nal, EF-hand domains are separated by a central domain consisting of four repeats of a 122-residne sequence. 

If weak complexes present in solution consist of dimers alone (Fig. 7), association patterns of homodimers (11 and 13) are of the head-to-tail type, that of heterodimer (72) being of the head-to-head type, since the two acylurea bonds in 1 and 2 extend... 

TMD and NBF (Fig. 1). Therefore, these transporters are termed half transporter (in contrast to full transporter) however, to achieve functional activity they have to form hetero- or homodimers. 

Recent studies indicate that - like many other receptors - G-protein-coupled receptors may form dimers, either homodimers or dimers with another type of receptor. The role of dimer formation in the cell surface expression of receptors and in their signalling and the resultant pharmacology are currently under intensive investigation [1]. 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

The two isozymes are both homodimers, composed of approximately 600 amino acids and possess approximately 60% homology. The three-dimensional structures of COX-1 and COX-2 are very similar. Each one consists of three independent units an epidermal growth factor-like domain, a membrane-binding section and an enzymic domain. The catalytic sites and the residues immediately adjacent are identical but for two small but crucial variations that result in an increase in the volume of the COX-2-active site, enabling it to accept inhibitor-molecules larger than those that could be accommodated in the COX-1 molecule. 

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

ECEs are metalloproteinases that are homologous to the neutral endopeptidase (NEP, E-24.11, neprilysin) unlike NEP, however, they form disulfide-bonded homodimers. In man, with ECE-1 and ECE-2, two isoforms are known, which are encoded by two separate genes. For ECE-1 four different variants have been identified (ECE-1 a-d), which are generated by the use of alternative promoters (Table 2). The ECE-1 isoforms only differ in their N-terminal amino acid sequence. For ECE-2, a single gene product has been described in... 

There is abundant experimental evidence suggesting that many (if not most) GPCRs exist as homodimers and/or heterodimers [4]. The functional significance of dimers and their role in G protein activation remains to be determined for most GPCRs. Experimental evidence suggests that dimers may play roles in processing and maturation of newly synthesized receptor protein. Heterodimers may contribute to pharmacologic... 

PDGF Isoforms consist of homo- and heterodimers of A- and B-polypeptide chains and homodimers of C- and D-polypeptide chains PDGFR Consists of PDGFR a and (3 receptors Embryonic development, particularly in the formation of the kidney, blood vessels, and various mesenchymal tissues. Proliferation of connective tissues, glial and smooth muscle cells... 

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. 

In mammalia, seven different members encoded by distinct genes have been identified, all of which are activated by a distinct set of cytokines. Diversity in signaling is provided by variants of STAT proteins derived from either alternative splicing of RNA transcripts or proteolytic processing (e.g., STATs 1,3,4, and 5) and the ability of certain STATs to form both homodimers and heterodimers with each other. In response to inteiferon-y monomeric STAT1 dimerizes, while upon interferon-a stimulation a heterotrimeric complex consisting of STAT 1 and STAT2 with associated... 

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