N-terminal domain

Figure 6.20 Space-filling diagram illustrating the structural changes of CDK2 upon cyclin binding, (a) The active site is in a cleft between the N-terminal domain (blue) and the C-terminal domain (purple). In the inactive form this site is blocked by the T-loop.

Figure 8.6 The N-terminal domain of lambda repressor, which binds DNA, contains 92 amino acid residues folded into five a helices. Two of these, a2 (blue) and a3 (red) form a helix-turn-hellx motif with a very similar structure to that of lambda Cro shown In Figure 8.4. The complete repressor monomer contains in addition a larger C-termlnal domain. (Adapted from C. Pabo and M. Lewis, Nature 298 443-447, 1982.)...

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. 

The phosducin polypeptide chmn, of some 240 amino acids, is folded into two domains (Figure 13.16). The N-terminal domain is mostly a-helical and appears to be quite flexible since only a weak electron density is obtained in the structure determination. The actual path of the polypeptide chain from the end of helix to the beginning of helix Ba is tentative due to slight disorder. This region is close to serine 73 at the beginning of Ba, which also becomes disordered on phosphorylation. 

In the complex with Gpy the two phosducin domains do not interact with each other, instead they wrap around the edge and the top side of the p propeller, to form an extensive interaction surface (Figure 13.17). The N-terminal domain of phosducin interacts with all of the top loops of the p propeller including part of the surface of Cpythat interacts with Gq (Figures 13.15 and 13.17). This interface between phosducin s N-terminal domain and Gpy clearly precludes association of the latter with Gq. 

In the structure of unphosphorylated phosducin that binds to Gpy, Ser 73 points towards the flexible loop of phosducin and not towards Gpy it is, therefore, accessible on the surface for phosphorylation. Phosphorylation of Ser 73 cannot lead to the direct disruption of the phosducin/GpY interaction. Rather, the structure suggests that phosphorylation may lead to conformational changes in the N-terminal domain of phosducin, especially in the flexible loop region, that could weaken or alter the phosducin/GpY interface. 

Figure 14.15 Stmcture of the SI fragment of chicken myosin as a Richardson diagram (a) and a space-filling model (b). The two light chains are shown in magenta and yellow. The heavy chain is colored according to three proteolytic fragments produced by trypsin a 25-kDa N-terminal domain (green) a central 50-kDa fragment (red) divided by a cleft into a 50K upper and a 50K lower domain and a 20-kDa C-terminal domain (blue) that links the myosin head to the coiled-coil tail. The 50-kDa and 20-kDa domains both bind actin, while the 25-kDa domain binds ATP. [(b) Courtesy of 1. Rayment.]...

Figure 17.3 The polypeptide chain of lysozyme fiom hacteiiophage T4 folds into two domains. The N-terminal domain is of the a + P type, built up from two a helices (red) and a four-stranded antiparallel P sheet (green). The C-terminal domain comprises seven short a helices (brown and blue) in a rather irregular arrangement. (The last half of this domain is colored blue for clarity.)...

FIGURE 9.14 Glycophorin A spans the membrane of the hnman erythrocyte via a single ff-helical transmembrane segment. The C-terminns of the peptide, whose sequence is shown here, faces the cytosol of the erythrocyte the N-terminal domain is extracellnlar. Points of attachment of carbohydrate groups are indicated. 

Proteolysis of this precursor yields the active form, aerolysiu, which is responsible for the pathogenic effects of the bacterium in deep wound infectious and diarrheal diseases. Like hemolysin, aerolysiu monomers associate to form heptameric membrane pores. The three /3-strands that contribute to the formation of the heptameric pore are shown in red. The N-terminal domain (residues 1-80, yellow) is a small lobe that protrudes from the rest of the protein. 

Conti et al. (1996) solved the crystal structure of the P. pyralis luciferase at 2.0 A resolution. The protein is folded into two compact domains, a large N-terminal portion and a small C-terminal portion. The former portion consists of a /1-barrel and two /1-sheets. The sheets are flanked by a-helices to form an aflafia five-layered structure. The C-terminal portion of the molecule forms a distinct domain, which is separated from the N-terminal domain by a wide cleft. It is suggested that the two domains will close up in the course of the luminescence reaction. 

Y2 63 PRKAG2 569 N-terminal domain 1-247 Targetting Muscle 7q36... 

Y3 54 PRKAG3 328 N-terminal domain 1-171 Targetting Muscle 2q35... 

N-terminal domain is the least conserved region and contains the transactivation domain AF-1. 

Glycine receptor function is modulated by alcohols and anesthetics [4]. Amino acid residue al(S267) is critical for alcohol potentiation, as mutation to small residues (Gly, Ala) enhance, and mutation to large residues (His, Cys, Tyr) diminish the ethanol effect. Glycine recqrtor modulation by Zn2+ involves structural determinants located within the large N-terminal domain. Additional glycinergic modulators include neuroactive steroids and the anthelmintic, ivermectin, which activates glycine receptors by a novel, strychnine-insensitive mechanism. 

The nAChR is comprised of five subunits, each of which spans the lipid bilayer to create a water-filled pore or channel (Fig. la). Each subunit consists of four transmembrane segments, the second transmembrane segment (M2) lines the ion channel (Fig. lb). The extracellular N-terminal domain of every subunit... 

PRs also interact with other signaling pathways, which can, e.g., be regulated by phosphorylation. Independent of transcriptional activation of PR, progestins can activate cytoplasmic signaling molecules including SRC and downstream MAP kinase in mammalian cells via interaction by a specific polyproline motif in the N-terminal domain of PR. 

SNAREs is an acronym for soluble NSF acceptor protein receptors. They are a superfamily of small and mostly membrane-bound proteins that are distinguished by the presence of a conserved stretch of 60 amino acids referred to as a SNARE motif. With few exceptions, a single transmembrane domain is located adjacent to the SNARE motif at the C-terminal end. Many SNAREs possess in addition an independently folded N-terminal domain whose structures are more diverse. 

HIV integrase consists of three distinct domains. The N-terminal domain contains a HHCC motif that coordinates a zinc atom that is required for viral cDNA integration. Three highly conserved amino acids (D,D-35-E) are embedded in the core domain, which form the acidic catalytic triad coordinating one or possibly two divalent metals (Mn + or Mg +). The C-terminal domain (residues 213-288) is responsible for unspecific DNA binding and adopts an overall SH3 fold (Chiu and Davies 2004). The enzyme functions as a multimer and to this end all three domains can form homodimers. 

All elastic proteins contain distinct domains, of which at least one is made up of elastic repeat sequences, and they all contain cross-links between residues in either the nonelastic or elastic domains [9]. Previously, the Drosophila CGI5920 gene was tentatively identified as one encoding a resUin-like protein [31]. To prepare recombinant resilin, we chose to express the first exon of the Drosophila CG15920 gene [29], which encodes an N-terminal domain in the native protein comprising 17 copies of the putative elastic repeat motif GGRPSDSYGAPGGGN [31]. 

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