Aggregates homodimer

In contrast, it has been suggested that for HCLA bases of type B, the stereodifferentiation proceeds via a complex composed of a lithium amide dimer and one molecule of oxirane. Indeed, these bases are known to aggregate in solution to C2 symmetric homodimers of type 62, as shown by multinuclear ( C, Li, N) NMR for HCLA 57 (Figure 4) . ... 

H NM R spectra in apolar solvents are less informative. Broad unresolved signals indicate the presence of undefined species. Obviously, the multicydic structure does not allow the formation of regular dimers, which would lead to an unfavorable overlap of the loops, but the interaction via the urea functions creates irregular aggregates. This inability to form hydrogen-bonded homodimers can be exploited in further reactions, e.g., for the construction of multiple catenanes (see Section 5.5). 

Mammalian ferritins are heteropolymers of H- and L-chains. These subunits are very closely related, with an a-carbon rmsd of 0.5 A and 55% sequence identity conservation of primary sequence rises to 79% when considering those residues responsible for intersubunit interactions. Subunit assembly appears to take place via partially structured monomers associating to form fully structured homodimers, which then aggregate further. Upon chemical denaturation and refolding, heterodimers are rarely observed. ... 

Although all ultracentrifugation measurements were done in buffers which contained no excess zinc, bound zinc ions are required for the specific homodimer formation of ZDD as the apo form of the domain was shown to be unfolded and nonspecifically aggregated [5]. Atomic absorption spectroscopy of the samples in the buffers used for these experiments confirmed the expected stoichiometry of zincbinding. 

In some cases, it is desirable to have a pharmaceutical protein in an aggregated state because it is the bioactive form of the protein. An example of this is surfactant protein B (SP-B), a pulmonary surfactant protein necessary for normal lung function in neonatal infants. " The protein exists exclusively as a homodimer in which the monomers are linked by a disulfide bond. In studies investigating efficacy of the SP-B monomer compared with the dimer in transgenic mice, it was found that although the surfactant action was preserved in the monomeric form of the protein, altered lung hysteresis was noted. The authors concluded that SP-B dimerization is required for optimal lung function. 

IFNy is a homodimer (native IFNy is a monomeric glycoprotein, but the active moiety is a dimer, which interacts with a- and p-receptors causing their aggregation and subsequent activation) formed by antiparallel association of two sub-imits. Each subunit has six a-helices held together by short nonhelical sequences. There are no p-sheets. The subunits have a flattened elliptical shape, whereas the overafl structure of the dimer is globular. ... 

Apoptosis is caused by the release or activation of one or more BH3 domain-only proteins (Fig. 13.9c, step 1). These initiating B 13-only proteins bind to a cytosolic heterodimer containing a Bcl-2 protein (step 2) and displace a previously bound BH3-only protein, Bid, BIM or PUMA (step 3). In the case of Bid, dissociation from a partner such as Bcl-2 may be mediated by proteolysis of the Bid N-terminal 60 amino acid residues, creating truncated Bid (tBid), which activates an effector protein. The BH3-only proteins are therefore activators of apoptosis that displace effector proteins (BAK or BAX) from a non-Bcl-2 partner on the cytosolic surface of mitochondria and endoplasmic reticulum (step 4). For example, BAK is attached to an outer mitochondrial membrane channel protein in a healthy cell. An activating BH3-only protein displaces BAK, which then self-aggregates into homodimers that burrow a hole in the mitochondrial or endoplasmic reticular membrane, releasing the contents (step 5). 

ALAS was initially isolated and purified from mammalian sources in the 1970s [11, 12]. The instability of the enzyme, its tendency to form aggregates and the low amount of ALAS in mitochondria were the major factors that affected the development of purification procedures conducive to obtaining protein in sufficient amounts to address questions related to the structure and function of ALAS. Even the use of drugs known to induce hepatic ALAS, such as 2-allyl-2-isopropylacetamide and 3,5-di-carbethoxy-l,4-dihydrocollidine, did not increase substantially the yield of purified ALAS from drug-induced animals [58-61]. In all studies, ALAS has been identified as a homodimer with PLP as an essential cofactor [11-13, 61]. The initial studies on the binding of the PLP cofactor were per-... 

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