Journal of Biosciences

, Volume 32, Issue 1, pp 101–111 | Cite as

Peptide segments in protein-protein interfaces

  • Arumay Pal
  • Pinak ChakrabartiEmail author
  • Ranjit Bahadur
  • Francis Rodier
  • Joël Janin


An important component of functional genomics involves the understanding of protein association. The interfaces resulting from protein-protein interactions — (i) specific, as represented by the homodimeric quaternary structures and the complexes formed by two independently occurring protein components, and (ii) non-specific, as observed in the crystal lattice of monomeric proteins — have been analysed on the basis of the length and the number of peptide segments. In 1000 Å2 of the interface area, contributed by a polypeptide chain, there would be 3.4 segments in homodimers, 5.6 in complexes and 6.3 in crystal contacts. Concomitantly, the segments are the longest (with 8.7 interface residues) in homodimers. Core segments (likely to contribute more towards binding) are more in number in homodimers (1.7) than in crystal contacts (0.5), and this number can be used as one of the parameters to distinguish between the two types of interfaces. Dominant segments involved in specific interactions, along with their secondary structural features, are enumerated.


Binding site interfacial peptides peptide inhibitor protein-protein interactions specific and non-specific interactions 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aloy P, Böttcher B, Ceulemans H, Leutwein C, Mellwig C, Fischer S, Gavin A, Bork P, Superti-Furga G, Serrano L and Russell R B 2004 Structure-based assembly of protein complexes in yeast; Science 303 2026–2029PubMedCrossRefGoogle Scholar
  2. Argos P 1988 An investigation of protein subunits and domain interfaces; Protein Eng. 2 101–113PubMedCrossRefGoogle Scholar
  3. Arkin M R and Wells J A 2004 Small-molecule inhibitors of protein-protein interactions: progressing towards the dream; Nat. Ret. Drug Discov. 3 301–317CrossRefGoogle Scholar
  4. Atassi M Z 1984 Antigenic structures of proteins: their determination has revealed important aspects of immune recognition and generated strategies for synthetic mimicking of protein binding sites; Eur. J. Biochem. 145 1–20PubMedCrossRefGoogle Scholar
  5. Bahadur R P, Chakrabarti P, Rodier F and Janin J 2003 Dissecting subunit interfaces in homodimeric proteins; Proteins 53 708–719PubMedCrossRefGoogle Scholar
  6. Bahadur R P, Chakrabarti P, Rodier F and Janin J 2004 A dissection of specific and non-specific protein-protein interfaces; J. Mol. Biol. 336 943–955PubMedCrossRefGoogle Scholar
  7. Berman H M, Westbrook J, Feng Z, Gilliland G, Bhat T N, Weissig H, Shindyalov I N and Bourne P E 2000 The Protein Data Bank; Nucleic Acids Res. 28 235–242PubMedCrossRefGoogle Scholar
  8. Bogan A A and Thorn K S 1998 Anatomy of hot spots in protein interfaces; J. Mol. Biol. 280 1–9PubMedCrossRefGoogle Scholar
  9. Brinda K V, Kannan N and Vishveshwara S 2002 Analysis of homodimeric protein interfaces by graph-spectral methods; Protein Eng. 15 265–277PubMedCrossRefGoogle Scholar
  10. Carugo O and Argos P 1997 Protein-protein crystal-packing contacts; Protein Sci. 6 2261–2263PubMedCrossRefGoogle Scholar
  11. Chakrabarti P and Janin J 2002 Dissecting protein-protein recognition sites; Proteins 47 334–343PubMedCrossRefGoogle Scholar
  12. Chothia C and Janin J 1975 Principles of protein-protein recognition; Nature (London) 256 705–708CrossRefGoogle Scholar
  13. Crosio M P, Janin J and Jullien M 1992 Crystal packing in six crystal forms of pancreatic ribonuclease; J. Mol. Biol. 228 243–251PubMedCrossRefGoogle Scholar
  14. Dasgupta S, Iyer G H, Bryant S H, Lawrence C E and Bell J A 1997 Extent and nature of contacts between protein molecules in crystal lattices and between subunits of protein oligomers; Proteins 28 494–514PubMedCrossRefGoogle Scholar
  15. De S, Krishnadev O, Srinivasan N and Rekha N 2005 Interaction preferences across protein-protein interfaces of obligatory and non-obligatory components are different; BMC Struct. Biol. 5 15PubMedCrossRefGoogle Scholar
  16. Edwards A M, Kus B, Jansen R, Greenbaum D, Greenblatt J and Gerstein M 2002 Bridging structural biology and genomics: assessing protein interaction data with known complexes; Trends Genetics 18 529–536CrossRefGoogle Scholar
  17. Eisenberg D, Marcotte E M, Xenarios I and Yeates T O 2000 Protein function in the post-genomic era; Nature (London) 405 823–826CrossRefGoogle Scholar
  18. Fasan R, Dias R L A, Moehle K, Zerbe O, Vrijbloed J W, Obrecht D and Robinson J A 2004 Using a β-hairpin to mimic an α-helix: cyclic peptidomimetic inhibitors of the p53-HDM2 protein-protein interaction; Angew. Chem. Int. Ed. 43 (2109–2112CrossRefGoogle Scholar
  19. Gibbs J B 2000 Mechanism-based target identification and drug discovery in cancer research; Science 287 1969–1973PubMedCrossRefGoogle Scholar
  20. Glaser F, Steinberg D M, Vakser I A and Ben-Tal N 2001 Residue frequencies and pairing preferences at protein-protein interfaces; Proteins 43 89–102PubMedCrossRefGoogle Scholar
  21. Guharoy M and Chakrabarti P 2005 Conservation and relative importance of residues across protein-protein interfaces; Proc. Natl. Acad. Sci. USA 102 15447–15452PubMedCrossRefGoogle Scholar
  22. Janin J and Rodier F 1995 Protein-protein interaction at crystal contacts; Proteins 23 580–587PubMedCrossRefGoogle Scholar
  23. Jones S and Thornton J M 1996 Principles of protein-protein interactions; Proc. Natl. Acad. Sci. USA 93 13–20PubMedCrossRefGoogle Scholar
  24. Jones S and Thornton J M 1997 Analysis of protein-protein interaction sites using surface patches; J. Mol. Biol. 272 121–132PubMedCrossRefGoogle Scholar
  25. Kabsch W and Sander C 1983 Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features; Biopolymers 22 2577–2637PubMedCrossRefGoogle Scholar
  26. Lawrence M C and Colman P M 1993 Shape complementarity at protein/protein interfaces; J. Mol. Biol. 234 946–950PubMedCrossRefGoogle Scholar
  27. Lo Conte L, Chothia C and Janin J 1999 The atomic structure of protein-protein recognition sites; J. Mol. Biol. 285 2177–2198PubMedCrossRefGoogle Scholar
  28. Mazza C, Segreff A, Mattaj I W and Cusack S 2002 Largescale induced fit recognition of an m7GpppG cap analogue by the human nuclear cap-binding complex; EMBO J. 21 5548–5557PubMedCrossRefGoogle Scholar
  29. Mintseris J and Weng Z 2003 Atomic contact vectors in proteinprotein recognition; Proteins 53 629–639PubMedCrossRefGoogle Scholar
  30. Murray A J, Lewis S J, Barclay A N and Brady R L 1995 One sequence, two folds: a metastable structure of CD2; Proc. Natl. Acad. Sci. USA 92 7337–7341PubMedCrossRefGoogle Scholar
  31. Neuvirth H, Raz R and Schreiber G 2004 ProMate: a structure based prediction program to identify the location of protein-protein binding sites; J. Mol. Biol. 338 181–199PubMedCrossRefGoogle Scholar
  32. Nicholls A, Sharp K and Honig B 1991 Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons; Proteins 11 281–296PubMedCrossRefGoogle Scholar
  33. Ofran Y and Rost B 2003 Analysing six types of protein-protein interfaces; J. Mol. Biol. 325 377–387PubMedCrossRefGoogle Scholar
  34. Pawson T 1995 Protein modules and signalling networks; Nature (London) 373 573–580CrossRefGoogle Scholar
  35. Pisabarro M T and Serrano L 1996 Rational design of specific high-affinity peptide ligands for the Ab1-SH3 domain; Biochemistry 35 10634–10640PubMedCrossRefGoogle Scholar
  36. Ponstingl H, Henrick K and Thornton J M 2000 Discriminating between homodimeric and monomeric proteins in the crystalline state; Proteins 41 47–57PubMedCrossRefGoogle Scholar
  37. Rodier F, Bahadur R P, Chakrabarti P and Janin J 2005 Hydration of protein-protein interfaces; Proteins 60 30–45CrossRefGoogle Scholar
  38. Saha R P, Bahadur R P and Chakrabarti P 2005 Inter-residue contacts in proteins and protein-protein interfaces and their use in characterizing the homodimeric interface J. Proteome Res. 4 1600–1609PubMedCrossRefGoogle Scholar
  39. Takagi H, Kakuta Y, Okada T, Yao M, Tanaka I and Kimura M 2005 Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects; Nat. Struct. Mol. Biol. 12 327–331PubMedCrossRefGoogle Scholar
  40. Toogood P L 2002 Inhibition of protein-protein association by small molecules: approaches and progress; J. Med. Chem. 45 1543–1558PubMedCrossRefGoogle Scholar
  41. Tsai C J, Lin S L, Wolfson H J and Nussinov R 1997 Study of protein-protein interfaces: a statistical analysis of the hydrophobic effect; Protein Sci. 6 53–64PubMedCrossRefGoogle Scholar
  42. Young L, Jernigan R L and Covell D G 1994 A role for surface hydrophobicity in protein-protein recognition; Protein Sci. 3 717–729PubMedCrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2007

Authors and Affiliations

  • Arumay Pal
    • 1
  • Pinak Chakrabarti
    • 1
    Email author
  • Ranjit Bahadur
    • 1
    • 2
  • Francis Rodier
    • 3
  • Joël Janin
    • 2
    • 3
  1. 1.Department of BiochemistryBose InstituteCalcuttaIndia
  2. 2.Institut de Biochimie et Biologie Moléculaire et CellulaireUniversité Paris-SudOrsayFrance
  3. 3.Laboratoire d’Enzymologie et de Biochimie StructuralesUPR9063 CNRSGif-sur-YvetteFrance

Personalised recommendations