title: Identification of WD40 repeats by secondary structure-aided profile-profile alignment.
abstract: A WD40 protein typically contains four or more repeats of ~40 residues ended with the Trp-Asp dipeptide, which folds into β-propellers with four β strands in each repeat. They often function as scaffolds for protein-protein interactions and are involved in numerous fundamental biological processes. Despite their important functional role, the "velcro" closure of WD40 propellers and the diversity of WD40 repeats make their identification a difficult task. Here we develop a new WD40 Repeat Recognition method (WDRR), which uses predicted secondary structure information to generate candidate repeat segments, and further employs a profile-profile alignment to identify the correct WD40 repeats from candidate segments. In particular, we design a novel alignment scoring function that combines dot product and BLOSUM62, thereby achieving a great balance of sensitivity and accuracy. Taking advantage of these strategies, WDRR could effectively reduce the false positive rate and accurately identify more remote homologous WD40 repeats with precise repeat boundaries. We further use WDRR to re-annotate the Pfam families in the β-propeller clan (CL0186) and identify a number of WD40 repeat proteins with high confidence across nine model organisms. The WDRR web server and the datasets are available at http://protein.cau.edu.cn/wdrr/.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA. Electronic address: cwang@carnegiescience.edu.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: yndxb@126.com.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Center for Cancer Molecular Diagnosis, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Electronic address: hanlei_45@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research and Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: xdsu@pku.edu.cn.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Su
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: zidingzhang@cau.edu.cn.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Advanced Analytics Institute and Centre for Health Technologies, University of Technology Sydney, 81 Broadway, Sydney, NSW 2007, Australia. Electronic address: Jinyan.Li@uts.edu.au.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for Industrial Enzymes and Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; Infection and Immunity Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Faculty of Medicine, Monash University, Melbourne, VIC 3800, Australia; Monash Centre for Data Science, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia. Electronic address: jiangning.song@monash.edu.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Song
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D051379:Mice; D010363:Pattern Recognition, Automated; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D000071678:WD40 Repeats
keywords: Bioinformatics; Profile–profile alignment; Remote sequence homology; Secondary structure prediction; WD40 repeat