Home LiteratureArticle Details
PMID: 20603021 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

A comprehensive comparison of transmembrane domains reveals organelle-specific properties.

Cell ·Vol. 142 ·No. 1 ·2010-07-09 ·Pages 158-69

Sharpe HJ, Stevens TJ, Munro S

Abstract

The various membranes of eukaryotic cells differ in composition, but it is at present unclear if this results in differences in physical properties. The sequences of transmembrane domains (TMDs) of integral membrane proteins should reflect the physical properties of the bilayers in which they reside. We used large datasets from both fungi and vertebrates to perform a comprehensive comparison of the TMDs of proteins from different organelles. We find that TMDs are not generic but have organelle-specific properties with a dichotomy in TMD length between the early and late parts of the secretory pathway. In addition, TMDs from post-ER organelles show striking asymmetries in amino acid compositions across the bilayer that is linked to residue size and varies between organelles. The pervasive presence of organelle-specific features among the TMDs of a particular organelle has implications for TMD prediction, regulation of protein activity by location, and sorting of proteins and lipids in the secretory pathway.

MeSH Terms
Animals Cell Membrane/metabolism Golgi Apparatus/metabolism Humans Hydrophobic and Hydrophilic Interactions Membrane Proteins/chemistry,metabolism Organelles/metabolism Protein Structure, Tertiary Structural Homology, Protein
Chemicals
Membrane Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sharpe Hayley J
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Stevens Tim J
Munro Sean
References (68)
68 references, click to expand
  1. SNAREs--engines for membrane fusion.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43 PMID: 16912714
  2. Comparison of the predicted and observed secondary structure of T4 phage lysozyme.
    Biochim Biophys Acta. 1975 Oct 20;405(2):442-51 PMID: 1180967
  3. Coordinated protein sorting, targeting and distribution in polarized cells.
    Nat Rev Mol Cell Biol. 2008 Nov;9(11):833-45 PMID: 18946473
  4. How proteins adapt to a membrane-water interface.
    Trends Biochem Sci. 2000 Sep;25(9):429-34 PMID: 10973056
  5. Cholesterol and the Golgi apparatus.
    Science. 1993 Sep 3;261(5126):1280-1 PMID: 8362242
  6. Structural determinants of water permeability through the lipid membrane.
    J Gen Physiol. 2008 Jan;131(1):69-76 PMID: 18166626
  7. A unified hydrophobicity scale for multispan membrane proteins.
    Proteins. 2009 Jul;76(1):13-29 PMID: 19089980
  8. SherLoc: high-accuracy prediction of protein subcellular localization by integrating text and protein sequence data.
    Bioinformatics. 2007 Jun 1;23(11):1410-7 PMID: 17392328
  9. The CCPN data model for NMR spectroscopy: development of a software pipeline.
    Proteins. 2005 Jun 1;59(4):687-96 PMID: 15815974
  10. An elaborate classification of SNARE proteins sheds light on the conservation of the eukaryotic endomembrane system.
    Mol Biol Cell. 2007 Sep;18(9):3463-71 PMID: 17596510
  11. The multigenic sphingomyelin synthase family.
    J Biol Chem. 2006 Oct 6;281(40):29421-5 PMID: 16905542
  12. SNAREs prefer liquid-disordered over "raft" (liquid-ordered) domains when reconstituted into giant unilamellar vesicles.
    J Biol Chem. 2004 Sep 3;279(36):37951-5 PMID: 15226320
  13. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane.
    J Cell Biol. 1999 Aug 23;146(4):741-54 PMID: 10459010
  14. Locating proteins in the cell using TargetP, SignalP and related tools.
    Nat Protoc. 2007;2(4):953-71 PMID: 17446895
  15. NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D61-5 PMID: 17130148
  16. How protein transmembrane segments sense the lipid environment.
    Biochemistry. 2007 Feb 13;46(6):1457-65 PMID: 17279611
  17. Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles.
    J Mol Biol. 1983 May 15;166(2):211-7 PMID: 6854644
  18. Membrane lipids: where they are and how they behave.
    Nat Rev Mol Cell Biol. 2008 Feb;9(2):112-24 PMID: 18216768
  19. Lipid dynamics and lipid-protein interactions in rat enterocyte basolateral and microvillus membranes.
    Biochemistry. 1980 Jun 10;19(12):2763-9 PMID: 6249340
  20. Protein transport from the late Golgi to the vacuole in the yeast Saccharomyces cerevisiae.
    Biochim Biophys Acta. 2005 Jul 10;1744(3):438-54 PMID: 15913810
  21. Modulation of lateral diffusion in the plasma membrane by protein density.
    Curr Biol. 2007 Mar 6;17(5):462-7 PMID: 17331726
  22. Emerging roles for lipids in shaping membrane-protein function.
    Nature. 2009 May 21;459(7245):379-85 PMID: 19458714
  23. Do more complex organisms have a greater proportion of membrane proteins in their genomes?
    Proteins. 2000 Jun 1;39(4):417-20 PMID: 10813823
  24. Helical extension of the neuronal SNARE complex into the membrane.
    Nature. 2009 Jul 23;460(7254):525-8 PMID: 19571812
  25. Molecular code for protein insertion in the endoplasmic reticulum membrane is similar for N(in)-C(out) and N(out)-C(in) transmembrane helices.
    Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15702-7 PMID: 18840693
  26. Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol.
    Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4083-8 PMID: 15016920
  27. Estimating the length of transmembrane helices using Z-coordinate predictions.
    Protein Sci. 2008 Feb;17(2):271-8 PMID: 18096645
  28. The hydrophobic moment detects periodicity in protein hydrophobicity.
    Proc Natl Acad Sci U S A. 1984 Jan;81(1):140-4 PMID: 6582470
  29. Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin.
    BMC Biol. 2009 Aug 13;7:50 PMID: 19678920
  30. The GxxxG motif: a framework for transmembrane helix-helix association.
    J Mol Biol. 2000 Feb 25;296(3):911-9 PMID: 10677291
  31. Lipid traffic: floppy drives and a superhighway.
    Nat Rev Mol Cell Biol. 2005 Mar;6(3):209-20 PMID: 15738987
  32. Membrane protein folding and stability: physical principles.
    Annu Rev Biophys Biomol Struct. 1999;28:319-65 PMID: 10410805
  33. Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver.
    J Cell Biol. 1984 Mar;98(3):991-1000 PMID: 6699096
  34. Deviations from standard atomic volumes as a quality measure for protein crystal structures.
    J Mol Biol. 1996 Nov 22;264(1):121-36 PMID: 8950272
  35. Apical protein transport.
    Cell Mol Life Sci. 2006 Nov;63(21):2491-505 PMID: 16927027
  36. Bilayer thickness and membrane protein function: an energetic perspective.
    Annu Rev Biophys Biomol Struct. 2007;36:107-30 PMID: 17263662
  37. Euk-mPLoc: a fusion classifier for large-scale eukaryotic protein subcellular location prediction by incorporating multiple sites.
    J Proteome Res. 2007 May;6(5):1728-34 PMID: 17397210
  38. Lipid sorting in epithelial cells.
    Biochemistry. 1988 Aug 23;27(17):6197-202 PMID: 3064805
  39. Inositol phosphorylceramide synthase is located in the Golgi apparatus of Saccharomyces cerevisiae.
    Mol Biol Cell. 2000 Jul;11(7):2267-81 PMID: 10888667
  40. TOPDB: topology data bank of transmembrane proteins.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D234-9 PMID: 17921502
  41. Signals for sorting of transmembrane proteins to endosomes and lysosomes.
    Annu Rev Biochem. 2003;72:395-447 PMID: 12651740
  42. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins.
    Annu Rev Biophys Biophys Chem. 1986;15:321-53 PMID: 3521657
  43. Rhomboid protease dynamics and lipid interactions.
    Structure. 2009 Mar 11;17(3):395-405 PMID: 19278654
  44. Experimentally determined hydrophobicity scale for proteins at membrane interfaces.
    Nat Struct Biol. 1996 Oct;3(10):842-8 PMID: 8836100
  45. Molecular code for transmembrane-helix recognition by the Sec61 translocon.
    Nature. 2007 Dec 13;450(7172):1026-30 PMID: 18075582
  46. Transmembrane domain-dependent partitioning of membrane proteins within the endoplasmic reticulum.
    J Cell Biol. 2008 Apr 7;181(1):105-18 PMID: 18391072
  47. Recognition of transmembrane helices by the endoplasmic reticulum translocon.
    Nature. 2005 Jan 27;433(7024):377-81 PMID: 15674282
  48. An analysis of the size selectivity of solute partitioning, diffusion, and permeation across lipid bilayers.
    Biophys J. 1999 Sep;77(3):1268-83 PMID: 10465741
  49. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.
    J Mol Biol. 2001 Jan 19;305(3):567-80 PMID: 11152613
  50. LOCATE: a mammalian protein subcellular localization database.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D230-3 PMID: 17986452
  51. Molecular anatomy of a trafficking organelle.
    Cell. 2006 Nov 17;127(4):831-46 PMID: 17110340
  52. Transport through the Golgi apparatus by rapid partitioning within a two-phase membrane system.
    Cell. 2008 Jun 13;133(6):1055-67 PMID: 18555781
  53. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  54. Which in vitro models could be best used to study hepatocyte polarity?
    Biol Cell. 2008 Jul;100(7):387-98 PMID: 18549352
  55. Structure and origin of ordered lipid domains in biological membranes.
    J Membr Biol. 1998 Jul 15;164(2):103-14 PMID: 9662555
  56. Models of lipid-protein interactions in membranes.
    Annu Rev Biophys Biomol Struct. 1993;22:145-71 PMID: 8347987
  57. Comparative analysis of amino acid distributions in integral membrane proteins from 107 genomes.
    Proteins. 2005 Sep 1;60(4):606-16 PMID: 16028222
  58. ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
    Nat Biotechnol. 2006 Jul;24(7):841-7 PMID: 16823372
  59. The organizing potential of sphingolipids in intracellular membrane transport.
    Physiol Rev. 2001 Oct;81(4):1689-723 PMID: 11581500
  60. WoLF PSORT: protein localization predictor.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W585-7 PMID: 17517783
  61. Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network.
    J Cell Biol. 2009 May 18;185(4):601-12 PMID: 19433450
  62. Glycosyltransferases. Structure, localization, and control of cell type-specific glycosylation.
    J Biol Chem. 1989 Oct 25;264(30):17615-8 PMID: 2681181
  63. The length of cargo-protein transmembrane segments drives secretory transport by facilitating cargo concentration in export domains.
    J Cell Sci. 2009 Jun 1;122(Pt 11):1759-67 PMID: 19435807
  64. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  65. Segregation of glucosylceramide and sphingomyelin occurs in the apical to basolateral transcytotic route in HepG2 cells.
    J Cell Biol. 1997 Apr 21;137(2):347-57 PMID: 9128247
  66. Lipid traffic in animal cells.
    Annu Rev Cell Biol. 1989;5:247-75 PMID: 2688705
  67. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  68. MUSCLE: multiple sequence alignment with high accuracy and high throughput.
    Nucleic Acids Res. 2004 Mar 19;32(5):1792-7 PMID: 15034147
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.05.037
Published
2010-07-09
Pages
158-69
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2928124
Subset
IM
Grants
Medical Research Council · MC_U105178783 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.cell.2010.05.037 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2