A Structural-alphabet-based Strategy for Finding Structural Motifs Across Protein Families

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2010 Jun 8

PMID 20525797

Citations 14

Authors

Chih Yuan Wu

Yao Chi Chen

Carmay Lim

Affiliations

Soon will be listed here.

Abstract

Proteins with insignificant sequence and overall structure similarity may still share locally conserved contiguous structural segments; i.e. structural/3D motifs. Most methods for finding 3D motifs require a known motif to search for other similar structures or functionally/structurally crucial residues. Here, without requiring a query motif or essential residues, a fully automated method for discovering 3D motifs of various sizes across protein families with different folds based on a 16-letter structural alphabet is presented. It was applied to structurally non-redundant proteins bound to DNA, RNA, obligate/non-obligate proteins as well as free DNA-binding proteins (DBPs) and proteins with known structures but unknown function. Its usefulness was illustrated by analyzing the 3D motifs found in DBPs. A non-specific motif was found with a 'corner' architecture that confers a stable scaffold and enables diverse interactions, making it suitable for binding not only DNA but also RNA and proteins. Furthermore, DNA-specific motifs present 'only' in DBPs were discovered. The motifs found can provide useful guidelines in detecting binding sites and computational protein redesign.

Citing Articles

Entropy Analysis of Protein Sequences Reveals a Hierarchical Organization.

Anashkina A, Petrushanko I, Ziganshin R, Orlov Y, Nekrasov A Entropy (Basel). 2021; 23(12).

PMID: 34945953 PMC: 8700119. DOI: 10.3390/e23121647.

Knowledge-based prediction of protein backbone conformation using a structural alphabet.

Vetrivel I, Mahajan S, Tyagi M, Hoffmann L, Sanejouand Y, Srinivasan N PLoS One. 2017; 12(11):e0186215.

PMID: 29161266 PMC: 5697859. DOI: 10.1371/journal.pone.0186215.

Protein flexibility in the light of structural alphabets.

Craveur P, Joseph A, Esque J, Narwani T, Noel F, Shinada N Front Mol Biosci. 2015; 2:20.

PMID: 26075209 PMC: 4445325. DOI: 10.3389/fmolb.2015.00020.

Homopharma: a new concept for exploring the molecular binding mechanisms and drug repurposing.

Chiu Y, Tseng J, Liu K, Lin C, Hsu K, Yang J BMC Genomics. 2014; 15 Suppl 9:S8.

PMID: 25521038 PMC: 4290623. DOI: 10.1186/1471-2164-15-S9-S8.

Use of a structural alphabet to find compatible folds for amino acid sequences.

Mahajan S, de Brevern A, Sanejouand Y, Srinivasan N, Offmann B Protein Sci. 2014; 24(1):145-53.

PMID: 25297700 PMC: 4282420. DOI: 10.1002/pro.2581.

References

Hutchinson E, Thornton J . PROMOTIF--a program to identify and analyze structural motifs in proteins. Protein Sci. 1996; 5(2):212-20. PMC: 2143354. DOI: 10.1002/pro.5560050204. View

Parkinson G, Gunasekera A, Vojtechovsky J, Zhang X, Kunkel T, Berman H . Aromatic hydrogen bond in sequence-specific protein DNA recognition. Nat Struct Biol. 1996; 3(10):837-41. DOI: 10.1038/nsb1096-837. View

Shanahan H, Garcia M, Jones S, Thornton J . Identifying DNA-binding proteins using structural motifs and the electrostatic potential. Nucleic Acids Res. 2004; 32(16):4732-41. PMC: 519102. DOI: 10.1093/nar/gkh803. View

White A, Ding X, vanderSpek J, Murphy J, Ringe D . Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex. Nature. 1998; 394(6692):502-6. DOI: 10.1038/28893. View

Chen Y, Wu C, Lim C . Predicting DNA-binding amino acid residues from electrostatic stabilization upon mutation to Asp/Glu and evolutionary conservation. Proteins. 2007; 67(3):671-80. DOI: 10.1002/prot.21366. View

Ferrer-Costa C, Shanahan H, Jones S, Thornton J . HTHquery: a method for detecting DNA-binding proteins with a helix-turn-helix structural motif. Bioinformatics. 2005; 21(18):3679-80. DOI: 10.1093/bioinformatics/bti575. View

Dudev M, Lim C . Discovering structural motifs using a structural alphabet: application to magnesium-binding sites. BMC Bioinformatics. 2007; 8:106. PMC: 1851716. DOI: 10.1186/1471-2105-8-106. View

Kristensen D, Chen B, Fofanov V, Ward R, Lisewski A, Kimmel M . Recurrent use of evolutionary importance for functional annotation of proteins based on local structural similarity. Protein Sci. 2006; 15(6):1530-6. PMC: 2242527. DOI: 10.1110/ps.062152706. View

Efimov A . A novel super-secondary structure of proteins and the relation between the structure and the amino acid sequence. FEBS Lett. 1984; 166(1):33-8. DOI: 10.1016/0014-5793(84)80039-3. View

10.

Lo C, Chang Y, Wright J, Chen S, Kan D, Lim C . Combined experimental and theoretical study of long-range interactions modulating dimerization and activity of yeast geranylgeranyl diphosphate synthase. J Am Chem Soc. 2009; 131(11):4051-62. DOI: 10.1021/ja808699c. View

11.

McDonald I, Thornton J . Satisfying hydrogen bonding potential in proteins. J Mol Biol. 1994; 238(5):777-93. DOI: 10.1006/jmbi.1994.1334. View

12.

Watson J, Laskowski R, Thornton J . Predicting protein function from sequence and structural data. Curr Opin Struct Biol. 2005; 15(3):275-84. DOI: 10.1016/j.sbi.2005.04.003. View

13.

Pugalenthi G, Suganthan P, Sowdhamini R, Chakrabarti S . MegaMotifBase: a database of structural motifs in protein families and superfamilies. Nucleic Acids Res. 2007; 36(Database issue):D218-21. PMC: 2238926. DOI: 10.1093/nar/gkm794. View

14.

Luscombe N, Austin S, Berman H, Thornton J . An overview of the structures of protein-DNA complexes. Genome Biol. 2000; 1(1):REVIEWS001. PMC: 138832. DOI: 10.1186/gb-2000-1-1-reviews001. View

15.

Berman H, Battistuz T, Bhat T, Bluhm W, Bourne P, Burkhardt K . The Protein Data Bank. Acta Crystallogr D Biol Crystallogr. 2002; 58(Pt 6 No 1):899-907. DOI: 10.1107/s0907444902003451. View

16.

Lawson C, Carey J . Tandem binding in crystals of a trp repressor/operator half-site complex. Nature. 1993; 366(6451):178-82. DOI: 10.1038/366178a0. View

17.

Jones S, Barker J, Nobeli I, Thornton J . Using structural motif templates to identify proteins with DNA binding function. Nucleic Acids Res. 2003; 31(11):2811-23. PMC: 156721. DOI: 10.1093/nar/gkg386. View

18.

Lin K, Wright J, Lim C . Conformational analysis of long spacers in PROSITE patterns. J Mol Biol. 2000; 299(2):537-48. DOI: 10.1006/jmbi.2000.3746. View

19.

de Brevern A, Etchebest C, Hazout S . Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Proteins. 2000; 41(3):271-87. DOI: 10.1002/1097-0134(20001115)41:3<271::aid-prot10>3.0.co;2-z. View

20.

Perry K, Mondragon A . Structure of a complex between E. coli DNA topoisomerase I and single-stranded DNA. Structure. 2003; 11(11):1349-58. DOI: 10.1016/j.str.2003.09.013. View