Linker region three-residue linkers

Our method of clustering based on a-carbon distances and in turn backbone and side chain torsions has demonstrated the existence of possible structural motifs within well defined linker regions. The method is not quite exhaustive to account for data outside the clusters and its limitadons arise due to non-standard way of defining limits of the clusters. Nevertheless, the method does seem to bring out the stmctural differences among various linkers. Our analyses on mainly -a proteins fiom the CATH database (results not shown here) has resulted in two major clusters of three residue linkers between helices (H-L3-H) and few of the helical proteins have same angle of orientation of helices within a cluster. We are yet to extend this observation to the unique data set of protein chains discussed in this paper. 

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.)...

The conserved linker between repeats III and IV is critical for fast inactivation. Cleavage of the III-IV linkage causes a strong reduction in the rate of inactivation. A cluster of three hydrophobic residues (IFM) in the linker is an essential component, probably serving as a hydrophobic latch to stabilize the inactivated state. Other parts of the a subunit are also involved in fast inactivation. Conformational changes in the P region contribute to the slow inactivation process. 

The uPAR protein was initially purified from lysates of phorbol ester-stimulated U937 cells by affinity chromatography using diisopropyl fluoro-phosphates (DFP)-inactivated uPA [53, 54]. uPAR is anchored in the plasma membrane by a glycosylphosphatidylinositol (GPI) moiety and it consists of 283 amino acids in its processed form [55, 56]. The protein is composed of three domains and each domain contains 90 amino acids. The domains are connected by linker regions with a length of 15-20 amino acids [57, 58]. The disulfide bonds in the N-terminal domain I have been experimentally determined and the pattern of cysteine residues in the sequence has revealed... 

Fig. 2.2 (A) Traxler/Bower Kinase inhibitor pharmacophore. The perspective given is a top down view from the N-terminal to C-ter-minal domain in which the plane of the adenine ring matches that of the page. A short segment of the kinase linker region is shown which includes the three hydrogen bonding residues (minus side chains) plus the gatekeeper residue. In this orientation the top of...

A detailed sequence analysis revealed that coronin 1 (coronin 1 A) is made up of three distinct domains (see Fig. lA) The first, N terminal domain that also contains the 5 WD repeats is rich in p-sheet and is referred to as p-propeller (residues 1-355). The second domain is comprised of a region with little regular secondary structure and is referred to as linker domain (residues 356-429). Finally, the third domain is a coiled coil containing segment which is rich in a-helices (residues 430-461). ... 

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