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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite proline being assumed to be a helix-breaker, a large number of alpha-helices are found to contain Pro in globular as well as membrane proteins. Proline has no free NH group and therefore cannot form the conventional intra-helical NH.O=C hydrogen bond. An analysis of known protein structures has shown that the Cdelta protons are involved in C--H...O hydrogen bonds, usually two, with the carbonyl groups in the preceding turn of the helix (four and three residues away). These interactions satisfy the hydrogen bond forming potential of the carbonyl groups, which would otherwise, in the case of membrane-bound helices, be unfavorably exposed to hydrophobic surroundings. Depending on the type (based on the location of the carbonyl group, usually three, four or five residues preceding Pro) of C--H...O interactions, the kink in the helix may be of different magnitude. The puckering (UP or DOWN) of the pyrrolidine ring of Pro residues is controlled by the type of the C--H...O bond present, and the form that provides a better hydrogen bond geometry is preferred.
J Mol Biol 1998 Dec 11
PMID:C--H...O hydrogen bond involving proline residues in alpha-helices. 983 10

The eight-stranded antiparallel beta-barrel domain of the OmpA protein from Escherichia coli serves as a paradigm for the study of membrane assembly of integral beta-structured membrane proteins. Previous studies have shown that neither the periplasmic turns nor the surface-exposed loops contain topogenic information. Consequently, the question of whether any structural constraint is imposed onto individual transmembrane beta-strands is now addressed. To this end, amino acid sequences of beta-strands 4, 6 and 8 were randomized. In vivo membrane assembly of mutant proteins was assayed and 288 variants were sequenced. Three parameters were found to be important for efficient membrane assembly. (i) At least four of five randomized residues with side-chains pointing towards the lipid bilayer must be hydrophobic and none of the three central residues must be charged. (ii) Side-chains pointing into the beta-barrel interior must not be enlarged too much, possibly because of packing constraints. (iii) Proline residues are, in general, hardly tolerated in the transmembrane beta-strands.
J Mol Biol 1999 Jan 29
PMID:Membrane assembly of the Escherichia coli outer membrane protein OmpA: exploring sequence constraints on transmembrane beta-strands. 991 13

Ferritin from the liver of fresh, salt and brackish water fishes was purified by thermal denaturation of liver homogenate followed by ammonium sulphate fractionation and Sephacryl S-300 gel filtration. Yield and iron content of purified fish ferritins were 0.016-0.026 mg/g of wet tissue and 4-14%, respectively. The iron content of ferritins from marine and brackish species was higher than from fresh water species. The phosphate/iron ratio ranged from 0.5 to 1.8 and was higher than mammalian ferritins. The fish ferritins have 5-6% neutral carbohydrate. Native gel electrophoresis and molecular weight analysis revealed the presence of a monomeric ferritin. SDS-gel electrophoresis and immunoblotting showed a single protein band of 21 kDa suggesting the presence of similar sized subunits in the native structure of fish ferritins. Isoelectric focusing revealed microheterogeneity with five to seven bands of pI values between 4.1 and 7.0. Variations in the amino acid composition were observed. Proline and arginine were not detected in murrel and salmon species, respectively. High proline and low tyrosine contents were recorded for perch ferritin. Immunological studies by non-competitive indirect ELISA revealed varying degrees of cross-reactivity. Mammalian ferritins exhibited a moderate cross-reactivity with anti-fish ferritin. On the contrary, very low or no cross-reactivity was observed between fish ferritin and anti-mammalian ferritin. Ferritins from bony fishes such as murrel and rohu exhibited a high degree of cross-reactivity with anti-shark ferritin. However, a moderate cross-reactivity was observed between shark and anti-murrel ferritin. Ferritin from marine bony fishes, salmon and mackerel and perch (brackish) showed a low to very low cross-reactivity with both the antisera.
Comp Biochem Physiol B Biochem Mol Biol 1999 Jul
PMID:Purification and characterization of fish liver ferritins. 1048 Dec 57

We have isolated a cDNA from Aedes aegypti that is transcribed in the larval midgut in response to metal exposure, and in the adult female midgut in response to iron or cadmium exposure, or a blood meal. The cDNA encodes a protein, designated Aedes aegypti intestinal mucin 1 (AEIMUC1), which has similarities with invertebrate intestinal mucins and peritrophins, and vertebrate mucins. Proline, serine and threonine comprise 30% of the amino acid composition of AEIMUC1, a characteristic of mucins. AEIMUC1 contains three cysteine-rich domains, two of which flank a proline/serine/threonine-rich domain, a feature shared by many mucin genes. This is the first report on the isolation of a metal-responsive gene from an aquatic insect.
Insect Mol Biol 2000 Aug
PMID:Molecular cloning and characterization of a metal responsive Aedes aegypti intestinal mucin cDNA. 1097 19

Protein phosphorylation on serine or threonine residues preceding proline (Ser/Thr-Pro) plays an essential role for regulating various cellular processes, including cell cycle progression. Although phosphorylation has been proposed to regulate the function of a protein by inducing conformational changes, much less is known about what phosphate additions actually do and how the functions of phosphoproteins are coordinated. Proline is important for determining protein structure because it exists in cis or trans conformation and can put kinks into a polypeptide chain. We have shown that phosphorylation on Ser/Thr-Pro motifs reduces the cis/trans isomerization rate of Ser/Thr-Pro bonds. At the same time, proteins containing phosphorylated Ser/Thr-Pro motifs are substrates for the prolyl isomerase Pin1. The WW domain of Pin1 acts as a phosphoserine/threonine-binding module binding a defined subset of mitosis-specific phosphoproteins, such as Cdc25 and tau. These interactions target the enzymatic activity of Pin1 close to its substrates. In contrast to other prolyl isomerases (peptidyl-prolyl isomerases, PPlases), Pin1 has an extremely high degree of substrate specificity, specifically isomerizing phosphorylated Ser/Thr-Pro bonds. Therefore, Pin1 binds and regulates the function of a defined subset of phosphoproteins. Furthermore, inhibiting Pin1 function is lethal for dividing cells. Interestingly, Pin1, which can restore the biological function of phosphorylated tau, is sequestered in the neurofibrillary tangles in Alzheimer's brains. Thus, we have proposed a novel signaling regulatory mechanism, where protein phosphorylation creates binding sites for Pin1, which can then latch on to and isomerize the phosphorylated Ser/Thr-Pro peptide bond. In turn, this may change the shape of the protein, regulating its activity, dephosphorylation, degradation or location in the cell. This new post-phosphorylation regulatory mechanism appears to play an important role in normal cell function, such as mitotic progression, and in the pathogenesis of some human pathologies, such as Alzheimer's disease.
Cell Mol Life Sci 1999 Nov 30
PMID:Phosphorylation-dependent prolyl isomerization: a novel signaling regulatory mechanism. 1121 39

Proline residues occur frequently in transmembrane alpha helices, which contrasts with their behaviour as helix-breakers in water-soluble proteins. The three membrane-embedded proline residues of bacteriorhodopsin have been replaced individually by alanine and glycine to give P50A, or P50G on helix B, P91A, or P91G on helix C, and P186A or P186G on helix F, and the effect on the protein folding kinetics has been investigated. The rate-limiting apoprotein folding step, which results in formation of a seven transmembrane, alpha helical state, was slower than wild-type protein for the Pro50 and Pro91 mutants, regardless of whether they were mutated to Ala or Gly. These proline residues give rise to several inter-helix contacts, which are therefore important in folding to the seven transmembrane helix state. No evidence for cis-trans isomerisations of the peptidyl prolyl bonds was found during this rate-limiting apoprotein folding step. Mutations of all three membrane-embedded proline residues affected the subsequent retinal binding and final folding to bacteriorhodopsin, suggesting that these proline residues contribute to formation of the retinal binding pocket within the helix bundle, again via helix/helix interactions. These results point to proline residues in transmembrane alpha helices being important in the folding of integral membrane proteins. The helix/helix interactions and hydrogen bonds that arise from the presence of proline residues in transmembrane alpha helices can affect the formation of transmembrane alpha helix bundles as well as cofactor binding pockets.
J Mol Biol 2001 Apr 27
PMID:Proline residues in transmembrane alpha helices affect the folding of bacteriorhodopsin. 1132 78

A. L. Bayer, A. G. Ferguson, P. A. Lucchesi and A. M. Samarel. PYK2 Expression and Phosphorylation in Neonatal and Adult Cardiomyocytes. Journal of Molecular and Cellular Cardiology (2001) 33, 1017-1030. Proline-rich tyrosine kinase (PYK2) is a Ca(2+)-dependent, non-receptor protein tyrosine kinase involved in growth factor signaling. Although PYK2 is expressed in a variety of tissues, it has not yet been identified in cardiac muscle. Therefore, immunocytochemical and Western blotting techniques were used to examine PYK2 expression and phosphorylation in neonatal and adult rat ventricular cardiomyocytes (NRVM and ARVM, respectively). PYK2 concentration was much greater in neonatal, than in adult ventricular tissue and cardiomyocytes. In cultured cells, PYK2 expression was highly dependent on [Ca(2+)](i)transients and contractile activity. Non-contracting, low-density NRVM in serum-free culture expressed very low levels of PYK2, while high-density, spontaneously contracting NRVM showed a approximately 12-fold increase in PYK2 expression. Conversely, high-density NRVM treated with nifedipine (10 microM, 48 h) to block spontaneous [Ca(2+)](i)transients and contractile activity resulted in a 2.6-fold decrease in PYK2 levels. Similarly, overnight culture of quiescent ARVM markedly reduced PYK2 levels. Chronic treatment (48 h) of cultured NRVM with the hypertrophic agonist endothelin-1 (ET) (10-300 n M) did not significantly increase PYK2 levels, but strongly shifted the ratio of phosphorylated to total PYK2, indicating that PYK2 phosphorylation accompanies cardiomyocyte hypertrophy. Endothelin-1 also acutely activated PYK2 in both cultured NRVM, and in freshly isolated ARVM. These results suggest that PYK2 is involved in the generation of certain aspects of cardiomyocyte hypertrophy.
J Mol Cell Cardiol 2001 May
PMID:Pyk2 expression and phosphorylation in neonatal and adult cardiomyocytes. 1134 23

We describe the recognition by Thermus thermophilus prolyl-tRNA synthetase (ProRSTT) of proline, ATP and prolyl-adenylate and the sequential conformational changes occurring when the substrates bind and the activated intermediate is formed. Proline and ATP binding cause respectively conformational changes in the proline binding loop and motif 2 loop. However formation of the activated intermediate is necessary for the final conformational ordering of a ten residue peptide ("ordering loop") close to the active site which would appear to be essential for functional tRNA 3' end binding. These induced fit conformational changes ensure that the enzyme is highly specific for proline activation and aminoacylation. We also present new structures of apo and AMP bound histidyl-tRNA synthetase (HisRS) from T. thermophilus which we compare to our previous structures of the histidine and histidyl-adenylate bound enzyme. Qualitatively, similar results to those observed with T. thermophilus prolyl-tRNA synthetase are found. However histidine binding is sufficient to induce the co-operative ordering of the topologically equivalent histidine binding loop and ordering loop. These two examples contrast with most other class II aminoacyl-tRNA synthetases whose pocket for the cognate amino acid side-chain is largely preformed. T. thermophilus prolyl-tRNA synthetase appears to be the second class II aminoacyl-tRNA synthetase, after HisRS, to use a positively charged amino acid instead of a divalent cation to catalyse the amino acid activation reaction.
J Mol Biol 2001 Jun 15
PMID:A succession of substrate induced conformational changes ensures the amino acid specificity of Thermus thermophilus prolyl-tRNA synthetase: comparison with histidyl-tRNA synthetase. 1139 74

In order to examine how the stabilization of thermophilic proteins affects their folding, we have characterized the folding process of Thermus thermophilus ribonuclease H using circular dichroism, fluorescence, and pulse-labeling hydrogen exchange. Like its homolog from Escherichia coli, this thermophilic protein populates a partially folded kinetic intermediate within the first few milliseconds of folding. The structure of this intermediate is similar to that of E.coli RNase H and corresponds remarkably well to a partially folded form that is populated at low levels in the native state of the protein. Proline isomerization appears to partly limit the folding of the thermophilic but not the mesophilic protein. Lastly, unlike other thermophilic proteins, which unfold much more slowly than their mesophilic counterparts, T.thermophilus RNase H folds and unfolds with overall rates similar to those of E.coli RNase H.
J Mol Biol 2002 Feb 15
PMID:Comparison of the folding processes of T. thermophilus and E. coli ribonucleases H. 1185 42

The PrnA transcriptional activator of Aspergillus nidulans binds as a dimer to CCGG-N-CCGG inverted repeats and to CCGG-6/7N-CCGG direct repeats. The binding specificity of the PrnA Zn cluster differs from that of the Gal4p/Ppr1p/UaY/Put3p group of proteins. Chimeras with UaY, a protein that strictly recognizes a CGG-6N-CCG motif, show that the recognition of the direct repeats necessitates the PrnA dimerization and linker elements, but the recognition of the CCGG-N-CCGG inverted repeats depends crucially on the PrnA Zn binuclear cluster and/or on residues amino-terminal to it. Three high-affinity sites in two different promoters have been visualized by in vivo methylation protection. Proline induction is essential for in vivo binding to these three sites but, as shown previously, not for nuclear entry. Simultaneous repression by ammonium and glucose does not affect in vivo binding to these high-affinity sites. PrnA differs from the isofunctional Saccharomyces cerevisiae protein Put3p, both in its unique binding specificity and in the requirement of induction for in vivo DNA binding.
Mol Microbiol 2002 Apr
PMID:PrnA, a Zn2Cys6 activator with a unique DNA recognition mode, requires inducer for in vivo binding. 1197 93


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