1 / 19

On the evolution of membrane proteins

On the evolution of membrane proteins. Homology detection Blast, PSIBLAST are they good ? SHRIMP (Bernsel, submitted) Evolution of TM-helices Internal duplications >50% of +6TM proteins. Problems with homology detection of TM proteins. Methods optimized on globular proteins

arlene
Télécharger la présentation

On the evolution of membrane proteins

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Arne Elofsson (arne@bioinfo.se) On the evolution of membrane proteins Homology detection Blast, PSIBLAST are they good ? SHRIMP (Bernsel, submitted) Evolution of TM-helices Internal duplications >50% of +6TM proteins

  2. Problems with homology detection of TM proteins Arne Elofsson (arne@bioinfo.se) • Methods optimized on globular proteins • High scoring false positives due to similarity between unrelated TM regions • Hedman et al, 1998 (Pmembr): • Fold recognition methods improve this fact • Globular detections improved by profile-profile (HMM-HMM) comparisons

  3. Profile-profile methods improve detection of membrane proteins Arne Elofsson (arne@bioinfo.se)

  4. Classification of GPCRs at 1% FPR Arne Elofsson (arne@bioinfo.se)

  5. How does TM proteins evolve Arne Elofsson (arne@bioinfo.se) • Mutation rates any differences in respect to the different compartments. • Few “multi-domain” membrane proteins • Many complexes • Internal symmetry

  6. Arne Elofsson (arne@bioinfo.se) Slower evolution in the membrane

  7. Internal duplications on sequence level Arne Elofsson (arne@bioinfo.se) Searched for internal duplication events in 87 prokaryotic genomes Out of 38,124 membrane proteins, 377 duplication events could be detected (~1%) Internal duplications has been hard to detect on sequence level α α α α α α X A B C J. Mol. Biol. 2004, 339:1-15

  8. Arne Elofsson (arne@bioinfo.se) Lactose Permease

  9. Arne Elofsson (arne@bioinfo.se) 1xqf (NH3-channel) Antiparallel duplication

  10. Arne Elofsson (arne@bioinfo.se) 12-TM chain from Cytochrome C-oxidase(Triplication)

  11. Internal symmetry in α-helical inner membrane proteins Arne Elofsson (arne@bioinfo.se) Antiparallel:LeuTSecYBtuCDAQP1GlpFAmtBClC H+/Cl- exchange transporterNhaA N 2-fold symmetry axis • Parallel to membrane • Odd number of TMH • Domains anti-parallel to each other • In plane with membrane • Even number of TMH • Domains parallel to each other C middle Parallel:LacYGlpTSav1866 ABC transporterAcrBEmrDADP/ATP carrier N C

  12. Arne Elofsson (arne@bioinfo.se) Many (most) proteins have internal duplications

  13. Arne Elofsson (arne@bioinfo.se) Duplications in TM proteins

  14. Arne Elofsson (arne@bioinfo.se) Both parallel and antiparallel duplications exist

  15. But in order to have antiparallel domains, they must be inserted with opposing topology! Arne Elofsson (arne@bioinfo.se) N C inside membrane outside N C • In order for an antiparallel symmetry to be explained by a duplication event, each subunit of the homodimer must be inserted with opposite topology • That implies that a sequence can have dual topology, be inserted either way in the membrane • Have been constructed in labs (Cell 62, 1135-1141 & Cell 77, 401-412)

  16. Hypothesis for antiparallel internal symmetry Arne Elofsson (arne@bioinfo.se) Nat. Struct. Mol. Biol. 2006, 13: 94-96

  17. Detection of internal duplications Arne Elofsson (arne@bioinfo.se) • Structural alignments • Finds most of the manually detected examples. • Sequence alignments • Sequence alignments do not find most. • Using SHRIMP about 80% can be found • Also finds a few extra. • Some problems defining exact duplication unit • Genome scanning • Ongoing.

  18. Acknowledgements Arne Elofsson (arne@bioinfo.se) • Erik Granseth • Anni Kauko • Jenny Falk • Andreas Bernsel • Kristoffer Illergård

  19. Arne Elofsson (arne@bioinfo.se) Final comments Thanks to EMBRACE Please fill out the questionaire..

More Related