Linker region

The apical domain (blue), which is a p sandwich flanked by a helices, is formed by the middle region of the polypeptide chain. The two linker regions between the equatorial and the apical domains form a small infermediate domain (purple) comprising three a helices. 

Figure 9.13 The DNA-binding region of the protein Oct-1, the POU region (green), comprises two domains, the POU-specific domain (dark green) and the POU homeodomain (light green) joined by a linker region (blue). These two domains bind to DNA in a tandem arrangement.

Figure 9.14 The two domains of the POU region bind in tandem on opposite sides of the DNA double helix. Both the POU-specific domain and the POU homeodomain have a helix-turn-helix motif (blue and red) which binds to DNA with their recognition helices (red) in the major groove. The linker region that joins these domains is partly disordered. (Adapted from J.D. Klemm et al.. Cell 77 21-32, 1994.)...

There is only one sequence-specific interaction with an amino acid side chain, which is provided by Lys 18 (red). The linker region is an extended chain that follows one strand of the DNA and provides several nonspecific contacts (blue) to the DNA. The numbering of the base pairs starts from the center of the DNA fragment. (Adapted from R. Matmorstein et al., Nature 356 408 14, 1992.)... 

DNA-binding site specificity among the C -zinc cluster family of transcription factors is achieved by the linker regions... 

Subsequently Stephen Harrison s group determined the x-ray structure of a PPRl-DNA complex and showed that the zinc cluster domain of PPRl and its mode of binding to DNA was very similar to that of GAL4, and that PPRl also dimerized through a coiled-coil region. However, the linker region... 

Figure 13.22 Hormone-receptor interactions involving the domain-domain linker region in the receptor, (a) Interactions between the growth hormone (red) and the growth hormone receptor (blue) linker region. Glu 127 of the receptor forms a salt bridge to Arg 167 in the hormone, (b) The same interaction area in the growth hormone (red)-prolactin receptor (green) complex. The displacement of the linker region due to differences in the domain orientations have brought Asp 124 in the prolactin receptor into contact with Arg 167 of the hormone. (Adapted from W. Somers et al.. Nature 372 478-481, 1994.)...

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)...

Figure 13.31 Space-filling diagram of Src tyrosine kinase in the same view as Figure 13.30. The SH2 domain makes only a few contacts with the rest of the molecule except for the tail region of the kinase. The SH3 domain contacts the N-domain of the kinase in addition to the linker region. There are extensive contacts between the N- and C-domains of the kinase. (Adapted from W. Xu et al., Nature 385 596-602, 1997.)...

Figure 13.32 Regulation of the catalytic activity of members of the Src family of tyrosine kinases, (a) The inactive form based on structure determinations. Helix aC is in a position and orientation where the catalytically important Glu residue is facing away from the active site. The activation segment has a conformation that through steric contacts blocks the catalytically competent positioning of helix aC. (b) A hypothetical active conformation based on comparisons with the active forms of other similar protein kinases. The linker region is released from SH3, and the activation segment changes its structure to allow helix aC to move and bring the Glu residue into the active site in contact with an important Lys residue.

Src tyrosine kinase contains both an SH2 and an SH3 domain linked to a tyrosine kinase unit with a structure similar to other protein kinases. The phosphorylated form of the kinase is inactivated by binding of a phosphoty-rosine in the C-terminal tail to its own SH2 domain. In addition the linker region between the SH2 domain and the kinase is bound in a polyproline II conformation to the SH3 domain. These interactions lock regions of the active site into a nonproductive conformation. Dephosphorylation or mutation of the C-terminal tyrosine abolishes this autoinactivation. 

Endonuclease-catalyzed hydrolysis of DNA at the internucleosomal linker regions into multimers of 180 base pairs which are visualized by electrophoresis as a ladder of nuclear DNA fragments. Access of the endonuclease to DNA is facilitated by depletion of polyamines, and the activity of the enzyme is mcrea.sed by and decreased by ADP-tibosylation. Thus, agents that increase intracellular Ca " or inhibit l>oly(ADP-ribose) polymerase can induce apoptosi.s. ... 

When the second-site revertants were segregated from the original mutations, the bci complexes carrying a single mutation in the linker region of the Rieske protein had steady-state activities of 70-100% of wild-type levels and cytochrome b reduction rates that were approximately half that of the wild type. In all these mutants, the redox potential of the Rieske cluster was increased by about 70 mV compared to the wild type (51). Since the mutations are in residues that are in the flexible linker, at least 27 A away from the cluster, it is extremely unlikely that any of the mutations would have a direct effect on the redox potential of the cluster that would be observed in the water-soluble fragments. However, the mutations in the flexible linker will affect the mobility of the Rieske protein. Therefore, the effect of the mutations described is due to the interaction between the positional state of the Rieske protein and its electrochemical properties (i.e., the redox potential of the cluster). 

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