Switch region

Comparison of prevalent repeat sequence units of mouse S regions 

purine Y, pyrimidine N, any nucleotide insertions or deletions shown in brackets. Data taken from [98] and [96], 

Each immunoglobulin class exists in two forms - as secreted and membrane-bound antibody. Membrane exons code for the transmembrane and cytoplasmic portion of membrane immunoglobulin and replace the secretory termini the transmembrane portion itself consists of a stretch of hydrophobic amino acids [107, 108,109,110,111,112,113], 

Mouse secretory termini of CH genes and structure of membrane exons (given in base pairs) 

intervening sequence between the last CH domain and the first membrane exon IVSm, intervening sequence between the membrane exons Ml and M2, membrane exons UT, untranslated region. For references see Fig. 4 and text. 

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Repressor and Cro proteins operate a procaryotic genetic switch region... 

How do repressor and Cro recognize the specific operator regions and achieve this subtle differential binding to the switch regions The sequences of ORl, 0R2, and OR3 in lambda are similar but not identical (Table 8.1). They are... 

Figure 13.6 Schematic diagram of Go. from transducin with a bound GTP analog. The polypeptide chain is organized Into two domains a catalytic domain (light red) with a structure similar to Ras, and a helical domain (green) which is an Insert in the loop between al and P2. There are three switch regions (violet) that have different conformations in the different catalytic states of Go.. The GTP analog (brown) Is bound to the catalytic domain in a cleft between the two domains. (Adapted from J. Noel et al.. Nature 366 654-663, 1993.)...

Ga is activated by conformational changes of three switch regions... 

Figure 13.15 Schematic diagram of the heterotrimeric Gap complex based on the crystal structure of the transducin molecule. The a suhunit is hlue with some of the a helices and (5 strands outlined. The switch regions of the catalytic domain of Gq are violet. The (5 suhunit is light red and the seven WD repeats are represented as seven orange propeller blades. The 7 subunit is yellow. The switch regions of Gq interact with the p subunit, thereby locking them into an inactive conformation that binds GDP but not GTP.

Binding to Gpy locks the flexible switch regions I and II of Ga into a conformation that firmly binds GDP but is nonproductive for GTP binding and hydrolysis. The replacement of GDP with GTP causes local but dramatic conformational changes to switch regions I and 11, as shown in the Go GTP-yS structure, which disrupt nearly all of the contacts between Gp. and Ga in the switch interface, thereby triggering release of Ga from Gpy (see Figures 13.10 and 13.11). 

Tetracycline has a secondary binding site in the H27 switch region that may also be fimctionally significant. The dtug binds at the interface of the three domains of 16S rRNA, close to helix 44 and between helices 11 and 27. As with the primary binding site, contacts are made from the hydrophilic face of the dtug to the backbone of 16S rRNA. In this binding site, tetracycline may function to stabilize the ram state. 

This functional form has no discontinuities, but there can be large derivatives at long distances if the switching region is short. 

Hanakahi LA, Dempsey LA, Li MJ, Maizels N (1997) Nucleolin is one component of die B cell-specific transcription factor and switch region binding protein, LRl. Proc Natl Acad Sci USA 94 3605-3610... 

Hanakahi LA, Maizels N (2000) Transcriptional activation by LRl at die Emu enhancer and switch region sites. Nucleic Acids Res 28 2651-2657... 

Fig. 5.12. Structure of the G-domain of the elongation factor EF-Tu from T. ther-mophilus with bonnd GppNHp, according to Berchthold et al., (1993). The non-hydrolysable analog GppNHp, the P loop and the switch regions I and II are shown, which play an important role in transition from the inactive GDP form to the active GTP form (see also 5.5.6 and 9.2.1). MOLSKRIPT representation according to Kranhs, (1991).

Firstly, it is assumed that the conformational changes in switch II triggered by GTP binding lead to dissociation of the Pycomplex. The Pycomplex binds to the switch regions I and II of the a-subunit. 

Highly resolved structures are also available for the G GDP Py-complex (Wall et al., 1995 Lambright et al., 1996). From these structures, the Py-complex binds in the region of the switch regions I and II and in the region of the N-terminus of the a-sub-... 

As a consequence of binding of the Py-complex, significant conformational changes are observed in the a-subimit. These affect, in particular, the switch regions I and II and the N-terminal a-helrx. 

Fig. 3. Structural features of heterotrimeric G proteins. Ribbon model of Gat/i(GDP)/f1y1 heterotrimer (1GOT), where a is blue, [I is green, and y is gold. The three Switch regions in Ga are highlighted in yellow, and GDP (red) is buried between the GTPase and helical domains of Ga. The subunits have been rotated outward to show the intersubunit interface, which is primarily composed of the aN helix (truncated in this view) and Switch II on Ga and blades 1-3 on GjS.

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