A reinforced merging methodology for mapping unique peptide motifs in members of protein familiesReport as inadecuate




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BMC Bioinformatics

, 7:38

First Online: 25 January 2006Received: 11 July 2005Accepted: 25 January 2006

Abstract

BackgroundMembers of a protein family often have highly conserved sequences; most of these sequences carry identical biological functions and possess similar three-dimensional 3-D structures. However, enzymes with high sequence identity may acquire differential functions other than the common catalytic ability. It is probable that each of their variable regions consists of a unique peptide motif UPM, which selectively interacts with other cellular proteins, rendering additional biological activities. The ability to identify and localize such UPMs is paramount in recognizing the characteristic role of each member of a protein family.

ResultsWe have developed a reinforced merging algorithm RMA with which non-gapped UPMs were identified in a variety of query protein sequences including members of human ribonuclease A RNaseA, epidermal growth factor receptor EGFR, matrix metalloproteinase MMP, and Sma-and-Mad related protein families Smad. The UPMs generally occupy specific positions in the resolved 3-D structures, especially the loop regions on the structural surfaces. These motifs coincide with the recognition sites for antibodies, as the epitopes of four monoclonal antibodies and two polyclonal antibodies were shown to overlap with the UPMs. Most of the UPMs were found to correlate well with the potential antigenic regions predicted by PROTEAN. Furthermore, an accuracy of 70% can be achieved in terms of mapping a UPM to an epitope.

ConclusionOur study provides a bioinformatic approach for searching and predicting potential epitopes and interacting motifs that distinguish different members of a protein family.

AbbreviationsGFPgreen fluorescent protein

EGFRepidermal growth factor receptor

mAbmonoclonal antibody

MBPmaltose binding protein, MMP, matrix metalloproteinase

MSAmultiple sequence alignment

RMAreinforced merging algorithms

RNAribonucleic acid

RNaseribonuclease

SmadSma-and-Mad related protein

TGF-βtransforming growth factor-β

UPMunique peptide motif

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2105-7-38 contains supplementary material, which is available to authorized users.

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Author: Hao-Teng Chang - Tun-Wen Pai - Tan-chi Fan - Bo-Han Su - Pei-Chih Wu - Chuan-Yi Tang - Chun-Tien Chang - Shi-Hwei Liu - Ma

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