Nucleotide-binding domains

ABC transporters use the energy of nucleotide hydrolysis to transport substances across membranes against a concentration gradient [14]. All ABC proteins have 

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Pai, E.F., et al. Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341 209-214,... 

Cyclic Nucleotide-binding Domain Cyclic Nucleotide Phosphodiesterases Cyclic Nucleotide-regulated Cation Channels Cyclic Nucleotides Cyclin... 

The headpiece contains five subdomains the N-terminal region (residues 1-40), the transduction or B domain (residues 131-238), the phosphorylation domain (residues 328-505), the nucleotide binding domain (residues 505-680) and the hinge domain (residues 681-738). The evidence supporting each of these assignments will be discussed in turn. 

The phosphorylation and nucleotide binding domains. The phosphorylation domain contains the phosphate acceptor Asp351, that is phos-phorylated by ATP during Ca " " transport [45,80,87,94,95]. Site-specific... 

The T1 cleavage site is at the boundary between the phosphorylation and nucleotide binding domains, while the T2 site demarcates the phosphorylation from the transduction or B domain. The separation into subdomains is presumed to enhance... 

Fig. 8. Mutagenesis of the predicted ATP binding site. ATP is shown in proximity to amino acids in four loops predicted to form the ATP binding site in the nucleotide binding domain [49,134] and a fifth loop representing the phosphorylation site at Asp351 [97], Mutations and the corresponding Ca transport activity of the mutants relative to wild-type are indicated. From Clarke et al. [103).

Approximately 90% of CF patients carry a loss-of-function CFTR mutation on at least one allele that results in deletion of phenylalanine 508 (F508del) in the first CFTR nucleotide-binding domain [7]. The F508del prevents the proper domain folding and assembly of the multidomain CFTR protein during its biogenesis in the endoplasmic... 

The ABC transporters are products of one of the largest gene superfamilies. Each consists of two cytoplasmic nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). The NBDs are highly conserved across the ABC family and contain motifs typical of ATP-binding sites, whereas the TMD structures vary, probably because they are adapted to the wide variety of substrates. In eukaryotes the C-terminal of each NBD is linked to a TMD. In some cases the functional unit is (NBD-TMD)2 and, in others, the first TMD is covalently linked to the second NBD. 

LTD long-term depression NBD nucleotide-binding domain... 

The Fe-protein has the protein fold and nucleotide-binding domain of the G-protein family of nucleotide-dependent switch proteins, which are able to change their conformation dependent on whether a nucleoside diphosphate (such as GDP or ADP) is bound instead of the corresponding triphosphate (GTP or ATP). However, nucleotide analogues, which induce the conformational switch of the Fe-protein, do not allow substrate reduction by the MoFe-protein, nor does reduction of the MoFe-protein by other electron-transfer reagents (whether small proteins or redox dyes) drive substrate reduction. Only the Fe-protein can reduce the MoFe-protein to a level that allows it to reduce substrates such as... 

Cui, J., Kagan, A., Qin, D., Mathew, J., Melman, Y.F. and McDonald, T.V. (2001) Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2. The Journal of Biological Chemistry, 276, 17244-17251. 

Lee, J.Y., Urbatsch, I.L., Senior, A.E. and Wilkens, S. (2002) Projection structure of P-glycoprotein by electron microscopy. Evidence for a closed conformation of the nucleotide binding domains. Journal of Biological Chemistry, 277, 40125-40131. 

Loo, T.W., Bartlett, M.C. and Clarke, D. M. (2002) The LSGGQ motif in each nucleotide-binding domain of human P-glycoprotein is adjacent to the opposing walker A sequence. Journal of Biological Chemistry, 277, 41303-41306. 

An important question arises about the effects of phospholipid composition and the function of membrane-bound enzymes. The phospholipid composition and cholesterol content in cell membranes of cultured cells can be modified, either by supplementing the medium with specific lipids or by incubation with different types of liposomes. Direct effects of phospholipid structure have been observed on the activity of the Ca2+-ATPase (due to changes in the phosphorylation and nucleotide binding domains) [37]. Evidence of a relationship between lipid structure and membrane functions also comes from studies with the insulin receptor [38]. Lipid alteration had no influence on insulin binding, but modified the kinetics of receptor autophosphorylation. 

Fig. 2. An example of a complex multidomain protein that includes both domain concatenation and intercalation. (A) See color insert. RASMOL view of phosphotransferase pyruvate kinase (pdb entry lpkn) colored to show the three identifiable domains. Blue is the j3 barrel regulatory domain, orange is an eightfold a/fi barrel, the catalytic substrate binding domain, and green is a central /3, a/(B nucleotide binding domain. Not displayed is the leader subsequence composed of a random coil and short helix. (B) Linear order along the sequence of these components.

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