Dataset Information

Pepitope: epitope mapping from affinity-selected peptides.

ABSTRACT: UNLABELLED:Identifying the epitope to which an antibody binds is central for many immunological applications such as drug design and vaccine development. The Pepitope server is a web-based tool that aims at predicting discontinuous epitopes based on a set of peptides that were affinity-selected against a monoclonal antibody of interest. The server implements three different algorithms for epitope mapping: PepSurf, Mapitope, and a combination of the two. The rationale behind these algorithms is that the set of peptides mimics the genuine epitope in terms of physicochemical properties and spatial organization. When the three-dimensional (3D) structure of the antigen is known, the information in these peptides can be used to computationally infer the corresponding epitope. A user-friendly web interface and a graphical tool that allows viewing the predicted epitopes were developed. Pepitope can also be applied for inferring other types of protein-protein interactions beyond the immunological context, and as a general tool for aligning linear sequences to a 3D structure. AVAILABILITY:http://pepitope.tau.ac.il/

SUBMITTER: Mayrose I

PROVIDER: S-EPMC7110138 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Pepitope: epitope mapping from affinity-selected peptides.

Mayrose Itay I Penn Osnat O Erez Elana E Rubinstein Nimrod D ND Shlomi Tomer T Freund Natalia Tarnovitski NT Bublil Erez M EM Ruppin Eytan E Sharan Roded R Gershoni Jonathan M JM Martz Eric E Pupko Tal T

Bioinformatics (Oxford, England) 20071031 23

<h4>Unlabelled</h4>Identifying the epitope to which an antibody binds is central for many immunological applications such as drug design and vaccine development. The Pepitope server is a web-based tool that aims at predicting discontinuous epitopes based on a set of peptides that were affinity-selected against a monoclonal antibody of interest. The server implements three different algorithms for epitope mapping: PepSurf, Mapitope, and a combination of the two. The rationale behind these algorit ...[more]

PMID: 17977889

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Project description:Autism spectrum disorder (ASD) is an important health issue and affects 1 in 59 children in the US. Prior studies determined that maternal autoantibody related (MAR) autism is thought to be associated with ~23% of ASD cases. We previously identified seven MAR-specific autoantigens including CRMP1, CRMP2, GDA, LDHA, LDHB, STIP1, and YBX1. We subsequently described the epitope peptide sequences recognized by maternal autoantibodies for each of the seven ASD-specific autoantigens. The aim of the current study was to expand upon our previous work and identify additional antigens recognized by the ASD-specific maternal autoantibodies, as well as to map the unique ASD-specific epitopes using microarray technology. Fetal Rhesus macaque brain tissues were separated by molecular weight and a fraction containing bands between 37 and 45 kDa was analyzed using 2-D gel electrophoresis, followed by peptide mass mapping using MALDI-TOF MS and TOF/TOF tandem MS/MS. Using this methodology, Neuron specific enolase (NSE) was identified as a target autoantigen and selected for epitope mapping. The full NSE sequence was translated into 15-mer peptides with an overlap of 14 amino acids onto microarray slides and probed with maternal plasma from mothers with an ASD child and from mothers with a Typically Developing child (TD) (ASD = 27 and TD = 21). The resulting data were analyzed by T-test. We found 16 ASD-specific NSE-peptide sequences for which four sequences were statistically significant (p < 0.05) using both the t-test and SAM t-test: DVAASEFYRDGKYDL (p = 0.047; SAM score 1.49), IEDPFDQDDWAAWSK (p = 0.049; SAM score 1.49), ERLAKYNQLMRIEEE (p = 0.045; SAM score 1.57), and RLAKYNQLMRIEEEL (p = 0.017; SAM score 1.82). We further identified 5 sequences that were recognized by both ASD and TD antibodies suggesting a large immunodominant epitope (DYPVVSIEDPFDQDDWAAW). While maternal autoantibodies against the NSE protein are present both in mothers with ASD and mothers of TD children, there are several ASD-specific epitopes that can potentially be used as MAR ASD biomarkers. Further, studies including analysis of NSE as a target protein in combination with the previously identified MAR ASD autoantigens are currently underway.

Project description:IntroductionHuman bone morphogenetic proteins (BMPs) constitute a large family of cytokines related to members of the transforming growth factor-β superfamily, which fulfill biological functions by specificity binding to their cognate type I (BRI) and type II (BRII) receptors through conformational wrist and linear knuckle epitopes, respectively.Methods and resultsWe systematically examined the intermolecular recognition and interaction between the BMP proteins and BRI receptor at structural, energetic and dynamic levels. The BRI-binding site consists of three hotspot regions on BMP surface, which totally contribute ~70% potency to the BMP-BRI binding events and represent the core sections of BMP conformational wrist epitope; the contribution increases in the order: hotspot 2 (~ 8%) < hotspot 3 (~ 20%) < hotspot 1 (~ 40%). Multiple sequence alignment and structural superposition revealed a consensus sequence pattern and a similar binding mode of the three hotspots shared by most BMP members, indicating a high conservation of wrist epitope in BMP family. The three hotspots are natively folded into wellstructured U-shaped,, loop and double-stranded conformations in BMP proteins, which, however, would become largely disordered when splitting from the protein context to derive osteogenic peptides in free state, thus largely impairing their rebinding capability to BRI receptor. In this respect, cyclization strategy was employed to constrain hotspot 1/3-derived peptides into a native-like conformation, which was conducted by adding a disulfide bond across the ending arms of linear peptides based on their native conformations. Fluorescence-based assays substantiated that the cyclization can effectively improve the binding affinities of osteogenic peptides to BRI receptor by 3-6-fold. The cyclic peptides also exhibit a good selectivity for BRI over BRII (> 5-fold), confirming that they can specifically target the wrist epitope-binding site of BRI receptor.ConclusionThe rationally designed cyclic peptides can be regarded as the promising lead entities that should be further chemically modified to enhance their in vivo biological stability for further bioengineering therapeutic osteogenic peptides against chondrocyte senescence and bone disorder.

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Pepitope: epitope mapping from affinity-selected peptides.

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Pepitope: epitope mapping from affinity-selected peptides.

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