A Noncanonical Binding Site in the EVH1 Domain of Vasodilator-Stimulated Phosphoprotein Regulates Its Interactions with the Proline Rich Region of Zyxin

AbstractHighly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.

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A Proline-Rich Region in the Zeste Protein Essential for Transvection and white Repression by Zeste1

Genetics ◽

10.1093/genetics/148.4.1865 ◽

1998 ◽

Vol 148 (4) ◽

pp. 1865-1874

Author(s):

Christina Rosen ◽

Dale Dorsett ◽

Joseph Jack

Keyword(s):

Dna Binding ◽

Protein Interactions ◽

Homologous Chromosome ◽

Protein Complexes ◽

Dna Binding Protein ◽

Polycomb Group ◽

The Self ◽

Rich Region ◽

Interaction Domain ◽

Proline Rich Region

Abstract The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.

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Map-based cloning of a gene sequence encoding a nucleotide-binding domain and a leucine-rich region at the Cre3 nematode resistance locus of wheat

Genome ◽

10.1139/g97-087 ◽

1997 ◽

Vol 40 (5) ◽

pp. 659-665 ◽

Cited By ~ 87

Author(s):

Evans S. Lagudah ◽

Odile Moullet ◽

Rudi Appels

Keyword(s):

Disease Resistance ◽

Gene Family ◽

Binding Site ◽

Resistance Gene ◽

Resistance Genes ◽

Gene Sequence ◽

Nucleotide Binding ◽

Disease Resistance Gene ◽

Leucine Rich Repeat ◽

Rich Region

The Cre3 gene confers a high level of resistance to the root endoparasitic nematode Heterodera avenae in wheat. A DNA marker cosegregating with H. avenae resistance was used as an entry point for map-based cloning of a disease resistance gene family at the Cre3 locus. Two related gene sequences have been analysed at the Cre3 locus. One, identified as a cDNA clone, encodes a polypeptide with a nucleotide binding site (NBS) and a leucine-rich region; this member of the disease resistance gene family is expressed in roots. A second Cre3 gene sequence, cloned as genomic DNA, appears to be a pseudogene, with a frame shift caused by a deletion event. These two genes, related to members of the cytoplasmic NBS – leucine rich repeat class of plant disease resistance genes were physically mapped to the distal 0.06 fragment of the long arm of wheat chromosome 2D and cosegregated with nematode resistance.Key words: cereal cyst nematode, disease resistance genes, nucleotide-binding site, leucine-rich repeat.

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Identification of amino acid residues required for a specific interaction between Src-tyrosine kinase and proline-rich region of phosphatidylinositol-3′ kinase

FEBS Letters ◽

10.1016/s0014-5793(96)01179-9 ◽

1996 ◽

Vol 397 (2-3) ◽

pp. 183-185 ◽

Cited By ~ 12

Author(s):

Paul Mak ◽

Zhiqing He ◽

Tomohiro Kurosaki

Keyword(s):

Amino Acid ◽

Tyrosine Kinase ◽

Specific Interaction ◽

Amino Acid Residues ◽

Phosphatidylinositol 3 Kinase ◽

Rich Region ◽

Src Tyrosine Kinase ◽

Proline Rich Region ◽

Phosphatidylinositol 3

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Identification and functional characterization of a novel human protein highly related to the yeast dynamin-like GTPase Vps1p

Journal of Cell Science ◽

10.1242/jcs.111.10.1341 ◽

1998 ◽

Vol 111 (10) ◽

pp. 1341-1349 ◽

Cited By ~ 3

Author(s):

M. Imoto ◽

I. Tachibana ◽

R. Urrutia

Keyword(s):

Endoplasmic Reticulum ◽

Cho Cells ◽

Mammalian Cells ◽

Functional Characterization ◽

Luciferase Reporter ◽

Pleckstrin Homology ◽

Rich Region ◽

Gtpase Domain ◽

Proline Rich Region

Dynamin proteins containing a GTPase domain, a pleckstrin homology motif and a proline-rich tail participate in receptor-mediated endocytosis in organisms ranging from insects to vertebrates. In addition, dynamin-related GTPases, such as the yeast Golgi protein Vps1p, which lack both the pleckstrin homology motif and the proline-rich region, participate in vesicular transport within the secretory pathway in lower eukaryotes. However, no data is available on the existence of Vps1p-like proteins in mammalian cells. In this study, we report the identification and characterization of a novel gene encoding a human dynamin-related protein, DRP1, displaying high similarity to the Golgi dynamin-like protein Vps1p from yeast and to a Caenorhabditis elegans protein deposited in the databank. These proteins are highly conserved in their N-terminal tripartite GTPase domain but lack the pleckstrin homology motif and proline-rich region. Northern blot analysis reveals that the DRP1 mRNA is detected at high levels in human muscle, heart, kidney and brain. Immunolocalization studies in Chinese hamster ovary (CHO) cells using an epitope-tagged form of DRP1 and confocal microscopy show that this protein is concentrated in a perinuclear region that labels with the endoplasmic reticulum marker DiOC6(3) and the Golgi marker C5-DMB-Cer. In addition, the localization of DRP1 is highly similar to the localization of the endoplasmic reticulum and cis-Golgi GTPase Rab1A, but not to the staining for the trans-Golgi GTPase Rab6. Furthermore, overexpression of a cDNA encoding a GTP binding site mutant of DRP1 (DRP1(K38E)) in CHO cells decreases the amount of a secreted luciferase reporter protein, whereas the overexpression of wild-type DRP1 increases the secretion of this marker. Together, these results constitute the first structural and functional characterization of a mammalian protein similar to the yeast dynamin-related GTPase Vps1p and indicate that the participation of these proteins in secretion has been conserved throughout evolution.

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A proline-rich region from maize γ-zein adopts a left-handed amphipathic structure that may act as a signal for its retention in the endoplasmic reticulum

Peptides 1994 ◽

10.1007/978-94-011-1468-4_19 ◽

1995 ◽

pp. 60-61 ◽

Cited By ~ 2

Author(s):

I. Dalcol ◽

F. Rabanal ◽

F. Albericio ◽

M. Pons ◽

M. Geli ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Rich Region ◽

Left Handed ◽

Proline Rich Region

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Three noncontiguous peptides comprise binding sites on high-molecular-weight kininogen to neutrophils

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.1.h145 ◽

1998 ◽

Vol 275 (1) ◽

pp. H145-H150 ◽

Cited By ~ 1

Author(s):

Mohammad M. H. Khan ◽

Satya P. Kunapuli ◽

Yingzhang Lin ◽

Abraham Majluf-Cruz ◽

Raul A. Dela Cadena ◽

...

Keyword(s):

Molecular Weight ◽

Binding Site ◽

High Molecular Weight ◽

Binding Sites ◽

Polymorphonuclear Leukocytes ◽

High Molecular Weight Kininogen ◽

Rich Region ◽

Putative Receptor ◽

Exon 9 ◽

Stimulation Of

The binding of high-molecular-weight kininogen (HK) to neutrophils (polymorphonuclear leukocytes, PMN) is required for the stimulation of aggregation and degranulation by human plasma kallikrein as well as the displacement of fibrinogen from this cell surface. The putative receptor for HK is the leukocyte integrin αMβ2, and domains 3 (D3) and 5 (D5) of HK form its binding site. To further map the binding sites on HK for PMN, we used D3 recombinant exon products and designed peptides from D3 and D5. In D3, a heptapeptide, Leu271-Ala277, from exon 7 product, and a peptide, Cys333-Cys352, from exon 9 product can inhibit binding of kininogen to PMN. Two contiguous peptides from D5 in the histidine-glycine-rich region, Gly442-Lys458and Phe459-Lys478, each inhibit the binding of HK to PMN. This study has thus delineated three noncontiguous surface-oriented sequences on HK, which together comprise all or most of the binding site for human PMN.

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