Novel bombesin-like peptide binding proteins from lung.

Abstract Designed armadillo repeat proteins (dArmRPs) bind extended peptides in a modular way. The consensus version recognises alternating arginines and lysines, with one dipeptide per repeat. For generating new binding specificities, the rapid and robust analysis by crystallography is key. Yet, we have previously found that crystal contacts can strongly influence this analysis, by displacing the peptide and potentially distorting the overall geometry of the scaffold. Therefore, we now used protein design to minimise these effects and expand the previously described concept of shared helices to rigidly connect dArmRPs and designed ankyrin repeat proteins (DARPins), which serve as a crystallisation chaperone. To shield the peptide-binding surface from crystal contacts, we rigidly fused two DARPins to the N- and C-terminal repeat of the dArmRP and linked the two DARPins by a disulfide bond. In this ring-like structure, peptide binding, on the inside of the ring, is very regular and undistorted, highlighting the truly modular binding mode. Thus, protein design was utilised to construct a well crystallising scaffold that prevents interference from crystal contacts with peptide binding and maintains the equilibrium structure of the dArmRP. Rigid DARPin-dArmRPs fusions will also be useful when chimeric binding proteins with predefined geometries are required.

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Structural diversity in twin-arginine signal peptide-binding proteins

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0703967104 ◽

2007 ◽

Vol 104 (40) ◽

pp. 15641-15646 ◽

Cited By ~ 54

Author(s):

J. Maillard ◽

C. A. E. M. Spronk ◽

G. Buchanan ◽

V. Lyall ◽

D. J. Richardson ◽

...

Keyword(s):

Signal Peptide ◽

Binding Proteins ◽

Peptide Binding ◽

Structural Diversity

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Novel soluble, high-affinity gastrin-releasing peptide binding proteins in Swiss 3T3 fibroblasts

Peptides ◽

10.1016/0196-9781(94)90062-0 ◽

1994 ◽

Vol 15 (6) ◽

pp. 993-1001 ◽

Cited By ~ 1

Author(s):

Madeleine A. Kane ◽

Lynda B. Portanova ◽

Kimberly Kelley ◽

Mark Holley ◽

Sherman E. Ross ◽

...

Keyword(s):

Binding Proteins ◽

Peptide Binding ◽

Gastrin Releasing Peptide ◽

High Affinity ◽

3T3 Fibroblasts ◽

Swiss 3T3 ◽

Swiss 3T3 Fibroblasts

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Analysis of β-Amyloid Peptide -Binding Proteins in Microglial Cells

The Open Geriatric Medicine Journal ◽

10.2174/1874827901205010001 ◽

2012 ◽

Vol 5 (1) ◽

pp. 1-6

Author(s):

Sachiko Ito

Keyword(s):

Binding Proteins ◽

Peptide Binding ◽

Amyloid Peptide ◽

Microglial Cells ◽

Β Amyloid ◽

Β Amyloid Peptide

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Faculty Opinions recommendation of The housekeeping dipeptide permease is the Escherichia coli heme transporter and functions with two optional peptide binding proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1040259.489196 ◽

2006 ◽

Author(s):

Tracy Palmer

Keyword(s):

Escherichia Coli ◽

Binding Proteins ◽

Peptide Binding

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The peptide transport system Opt is involved in both nutrition and environmental sensing during growth of Lactococcus lactis in milk

Microbiology ◽

10.1099/mic.0.048173-0 ◽

2011 ◽

Vol 157 (6) ◽

pp. 1612-1619 ◽

Cited By ~ 15

Author(s):

Mauld Lamarque ◽

Dominique Aubel ◽

Jean-Christophe Piard ◽

Christophe Gilbert ◽

Vincent Juillard ◽

...

Keyword(s):

Lactococcus Lactis ◽

Transport System ◽

Binding Proteins ◽

Peptide Binding ◽

Peptide Transport ◽

Dual Function ◽

Peptide Transporters ◽

Transport Mutants ◽

Dependent Transport ◽

Distinct Peptide

Lactococcus lactis is known to take up extracellular peptides via at least three distinct peptide transporters. The well-described oligopeptide transporter Opp alone is able to ensure the growth of L. lactis in milk, while the di- and tripeptide transporter DtpT is involved in a peptide-dependent signalling mechanism. The oligopeptide Opt transporter displays two peptide-binding proteins, OptA and OptS. We previously demonstrated that OptA-dependent transport is dedicated to nutritional peptides, as an optABCDF mutant (of a strain devoid of Opp) has an impaired capacity to grow in milk. Using isogenic peptide transport mutants, this study shows that biosynthesis of the Opt transporter is much less sensitive to downregulation that is dependent on extracellular peptides taken up by DtpT than is Opp biosynthesis; this peptide-dependent regulation relies on the transcriptional repressor CodY. We demonstrate the dual function of the Opt system; while OptA contributes to the bacterial nutrition during growth in milk, OptS is involved in the transport of signalling peptides derived from milk and controlling opp expression. So, these results shed new light on the peptide-dependent regulation relying on two peptide transporters with different specificities: DtpT and Opt (via OptS).

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Lyme Disease-Causing Borrelia Species Encode Multiple Lipoproteins Homologous to Peptide-Binding Proteins of ABC-Type Transporters

Infection and Immunity ◽

10.1128/iai.66.9.4115-4122.1998 ◽

1998 ◽

Vol 66 (9) ◽

pp. 4115-4122 ◽

Cited By ~ 20

Author(s):

Jon A. Kornacki ◽

Donald B. Oliver

Keyword(s):

Escherichia Coli ◽

Alkaline Phosphatase ◽

Lyme Disease ◽

Dna Hybridization ◽

Binding Proteins ◽

Cell Envelope ◽

Peptide Binding ◽

Amino Acid Sequences ◽

Linear Chromosome ◽

Homologous Genes

ABSTRACT To identify cell envelope proteins of Borrelia burgdorferi, the causative agent of Lyme disease, we constructed a library of B. burgdorferi genes fused to the Escherichia coli phoA gene, which expresses enzymatically active alkaline phosphatase. One such gene, oppA-1, encodes a predicted polypeptide with significant similarities to various peptide-binding proteins of ABC-type transporters. Immediately downstream of oppA-1 are two genes, oppA-2 and oppA-3, whose predicted polypeptide products show strong similarities in their amino acid sequences to OppA-1, including a sequence that resembles the most highly conserved region in peptide-binding proteins. By labeling with [3H]palmitate, OppA-1, OppA-2, and OppA-3 were shown to be lipoproteins. DNA hybridization analysis showed that the oppA-1 oppA-2 oppA-3 region is located on the linear chromosome of B. burgdorferi, and the genes are conserved among different Borrelia species that cause Lyme disease (B. burgdorferi, B. garinii, and B. afzelli), suggesting that all three homologous genes are important to the maintenance of Lyme disease spirochetes in one or more of their hosts.

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Advances in the design and engineering of peptide-binding repeat proteins

Biological Chemistry ◽

10.1515/hsz-2016-0233 ◽

2017 ◽

Vol 398 (1) ◽

pp. 23-29 ◽

Cited By ~ 7

Author(s):

Patrick Ernst ◽

Andreas Plückthun

Keyword(s):

Binding Proteins ◽

De Novo ◽

Peptide Binding ◽

Peptide Sequence ◽

Cellular Interactions ◽

Specific Recognition ◽

Repeat Proteins ◽

Biochemical Assays ◽

Selection Of ◽

Unstructured Regions

Abstract The specific recognition of peptides, which we define to include unstructured regions or denatured forms of proteins, is an intrinsic part of a multitude of biochemical assays and procedures. Many cellular interactions are also based on this principle as well. While it would be highly desirable to have a stockpile of sequence-specific binders for essentially any sequence, a de novo selection of individual binders against every possible target peptide sequence would be rather difficult to reduce to practice. Modular peptide binders could overcome this problem, as preselected and/or predesigned modules could be reused for the generation of new binders and thereby revolutionize the generation of binding proteins. This minireview summarizes advances in the development of peptide binders and possible scaffolds for their design.

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Functional roles and efficiencies of the thioredoxin boxes of calcium-binding proteins 1 and 2 in protein folding

Biochemical Journal ◽

10.1042/bj3570083 ◽

2001 ◽

Vol 357 (1) ◽

pp. 83-95 ◽

Cited By ~ 16

Author(s):

Barbara KRAMER ◽

David M. FERRARI ◽

Peter KLAPPA ◽

Nicole PÖHLMANN ◽

Hans-Dieter SÖLING

Keyword(s):

Calcium Binding ◽

Binding Proteins ◽

Peptide Binding ◽

Binding Activity ◽

Calcium Binding Proteins ◽

Carboxypeptidase Y ◽

Functional Roles ◽

Independent Process

The rat luminal endoplasmic-recticulum calcium-binding proteins 1 and 2 (CaBP1 and CaBP2 respectively) are members of the protein disulphide-isomerase (PDI) family. They contain two and three thioredoxin boxes (Cys-Gly-His-Cys) respectively and, like PDI, may be involved in the folding of nascent proteins. We demonstrate here that CaBP1, similar to PDI and CaBP2, can complement the lethal phenotype of the disrupted Saccharomyces cerevisiae PDI gene, provided that the natural C-terminal Lys-Asp-Glu-Leu sequence is replaced by His-Asp-Glu-Leu. Both the in vitro RNase AIII-re-activation assays and in vivo pro-(carboxypeptidase Y) processing assays using CaBP1 and CaBP2 thioredoxin (trx)-box mutants revealed that, whereas the three trx boxes in CaBP2 seem to be functionally equivalent, the first trx box of CaBP1 is significantly more active than the second trx box. Furthermore, only about 65% re-activation of denatured reduced RNase AIII could be obtained with CaBP1 or CaBP2 compared with PDI, and the yield of PDI-catalysed reactions was significantly reduced in the presence of either CaBP1 or CaBP2. In contrast with PDI, neither CaBP1 nor CaBP2 could catalyse the renaturation of denatured glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is a redox-independent process, and neither protein had any effect on the PDI-catalysed refolding of GAPDH. Furthermore, although PDI can bind peptides via its b′ domain, a property it shares with PDIp, the pancreas-specific PDI homologue, and although PDI can bind malfolded proteins such as ‘scrambled’ ribonuclease, no such interactions could be detected for CaBP2. We conclude that: (1) both CaBP2 and CaBP1 lack peptide-binding activity for GAPDH attributed to the C-terminal region of the a′ domain of PDI; (2) CaBP2 lacks the general peptide-binding activity attributed to the b′ domain of PDI; (3) interaction of CaBP2 with substrate (RNase AIII) is different from that of PDI and substrate; and (4) both CaBP2 and CaBP1 may promote oxidative folding by different kinetic pathways.

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