Structure subunits, domains

Asymmetric forms are present in high density at the neuromuscular junction. A second type of structural subunit, found primarily in the CNS, has a similar proline-rich attachment domain but contains covalently attached lipid, enabling this form of the enzyme to associate with cell membranes. The different C-termini and attachment modes lead to distinctive extracellular localizations of AChE but do not affect the intrinsic catalytic activities of the individual forms. 

Petegem, F.V., Clark, K.A., Chatelain, F.C. and Minor, D.L. (2004) Structure of a complex between a voltagegated calcium channel P subunit and an a-subunit domain. Nature 429, 671-675. 

Domain VI is homologous to domain IV of the large subunit, and therefore has five EF-hands motifs, four of which bind calcium while the fifth is involved in the interaction with the large subunit. The crystal structures of domain IV (Blanchard... 

Van Petegem F, Clark KA, Chatelain FC, Minor DL, Jr. (2004) Structure of a complex between a voltage-gated caldum channel beta-subunit and an alpha-subunit domain. Nature 429 671-5 Viard P, Butcher AJ, Halet G, Davies A, Numberg B, Heblich F, Dolphin AC (2004) PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane. Nat Neurosci 7 939 16... 

A major handicap to our detailed rmderstanding of the electron transfer reactions between TMADH and ETF is the lack of a crystallographic structure for ETF. Crystals of ETF have been isolated (White et al., 1994), but to date no structure for the protein has been reported. A homology model for ETF, however, has been constructed based on the crystallographic structure of human ETF (Roberts et al., 1996), and this model has been used to create a model of the electron transfer complex formed between TMADH and ETF (Chohan et al., 1998) (Figure 7). ETF comprises two subunits, which in turn form three domains. Domain I comprises the N-terminal region of the a-subunit, domain II comprises the C-terminal... 

All these results taken together allow us to visualize a likely mechanism for the catalytic cycle as a rotation in terms ofthe ye-subunit domain within the [a p]3in F, as illustrated in Fig. 33. After many enzyme turnovers and the rotation ofthe ye subunit domain has stopped, 1/3 ofthe ye subunit domains are expected to end up at each of the three a p pairs, consistent with the finding of approximately equal amounts of a 8 y, a 8 and a 5 e in the cross-linked products. The functional roles of these three small subunits will be discussed in Section I V.C. 1. below on the basis of their molecular structures. 

The subunit domain a b2 Ci2 in Fq is considered to be the site for proton translocation, but the details of the mechanism remain to be explored. It is generally agreed, however, that the a- and c-subunits mediate proton translocation, while the b-subunit only acts as a structural element to link F, (a3 p3) with Fq (the a-subunit). It is also known from the study of Schneider and Altendorf that all three subunits, a, b and c, are required for an active proton channel reconstituted in E. coli ATP synthase. In their experiment, these authors first dissociated, separated and purified the individual subunits and then integrated the subunits in all possible combinations into phospholipid vesicles. Each assembly was then tested for proton-translocation activity as well as its ability to bind to Fi, and it was found that functional activity could only be achieved by the combination a b2 Cio, the same combination that exists in native Fq. 

The catalytic subunit of PPl is a 37 kd single-domain protein. This subunit is usually bound to one of a family of regulatory subunits with masses ol approximately 120 kd in skeletal muscle and heart, the most prevalent regulatory subunit is called Gvr. whereas, in the liver, the most prevalent subunit is Gl. These regulatory subunits have modular structures with domains that participate in interactions with glycogen, with the catalytic subunit, and... 

Fig. 19. a The molecular structure of the E. coli amine oxidase dimer. In this view the dyad axis relating the two subunits is vertical in the plane of the page. One 80 kD subunit is colored red and the other is colored to identify domain structure. In this subunit domain D1 (residues 1-99) is grey, D2 (residues 100-185) is blue, D3 (residues 186-285) is magenta and the remainder of the subunit, comprising the /J-sandwich domain, is cyan. The locations of the active site coppers are indicated by green spheres. From [28] with permission... 

Arthropod hemocyanins (A-Hc) are proteins with molecular masses of up to 450 kD. They may be dissociated into six functional subunits of 75 kD mass, each of which contains a binuclear type 3 copper center responsible for oxygen binding. These proteins are, consequently, hexamers or multiple units thereof, which occur as native aggregates of 1 x 6,2 x 6,4 x 6, and 8x6 subunits. The latter have molecular masses of 3600 kD. The spider Eurypelma californicum possesses a hemocyanin structure of 4x6 [34]. These 24 subunits maybe classified into 7 different types a,b,c,d,e,f, and g, of which subunits a,d,e,f, and g occur 4 times, and the subunits b and c twice [236]. Each subunit has a specific position within the structure of the protein. Each protein subunit, i.e., the oxygen-binding unit, consists of three domains. Domains 1 (175 amino acids) and 2 (230 amino acids) have a pronounced a-helical structure, whereas domain 3 (250 amino acids) consist almost completely of /(-strands, which are arranged in a /(-barrel structure similar to that of Cu,Zn-SOD [34]. 

Diagram of the structure of deoxyhemocyanin from Panulirus interruptus at 3.2 A resolution (A) The hexameric arrangement of subunits (B) The domain structure of one subunit (C) The tertiary structure of domain 2, which contains the pair of copper atoms a-helices are represented by cylinders /3-strands by arrows, and copper atoms by diamonds (D) The active site and its histidine ligands. Reproduced with permission from B. Linzen, Science 229 (1985), 519-524. 

Fig. 8.3 Crystal structure of Complex III dimer and model of putative Complex III surface that interacts with Complex IV from S. cerevisiae. (A) Dimer of Complex III based on the crystal structure (figure adapted from (Hunte, 2005)) with the interface between monomers in the center. a-Helices of different subunits within the dimer are shown as rods of different shading connected by non-helical domains. Note the positions of CL and PE (all circled) in the center front (also on back center but not shown) between the dimers and on the front right) and back left) sides of the diagram. The two bars on the right show the 36-A width of the membrane. (B) The putative interface of Complex III monomer (figure adapted from (Pfeiffer et ah, 2003)) with Complex IV with the various subunit domains labeled. This view, with a cavity containing PE and CL (both circled), corresponds to the right and left sides of the view shown in (A) and is positioned within the membrane bilayer. Bottom of both diagrams faces the mitochondrial matrix...

Van Petegem F, Clark KA, Chatelain FC, Minor DL Jr. Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature 2004 429(6992) 671-5. 

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