A new in-silico method for determination of helical transmembrane domains based on the PepLook scan: application to IL-2Rβ and IL-2Rγc receptor chains

Charlois, Yan; Lins, Laurence; Brasseur, Robert
January 2011
BMC Structural Biology;2011, Vol. 11 Issue 1, p26
Academic Journal
Background: Modeling of transmembrane domains (TMDs) requires correct prediction of interfacial residues for insilico modeling and membrane insertion studies. This implies the defining of a target sequence long enough to contain interfacial residues. However, too long sequences induce artifactual polymorphism: within tested modeling methods, the longer the target sequence, the more variable the secondary structure, as though the procedure were stopped before the end of the calculation (which may in fact be unreachable). Moreover, delimitation of these TMDs can produce variable results with sequence based two-dimensional prediction methods, especially for sequences showing polymorphism. To solve this problem, we developed a new modeling procedure using the PepLook method. We scanned the sequences by modeling peptides from the target sequence with a window of 19 residues. Results: Using sequences whose NMR-structures are already known (GpA, EphA1 and Erb2-HER2), we first determined that the hydrophobic to hydrophilic accessible surface area ratio (ASAr) was the best criterion for delimiting the TMD sequence. The length of the helical structure and the Impala method further supported the determination of the TMD limits. This method was applied to the IL-2Rβ and IL-2RβTMD sequences of Homo sapiens, Rattus norvegicus, Mus musculus and Bos taurus. Conclusions: We succeeded in reducing the variation in the TMD limits to only 2 residues and in gaining structural information.


Related Articles

  • MEDELLER: homology-based coordinate generation for membrane proteins. Kelm, Sebastian; Jiye Shi; Deane, Charlotte M. // Bioinformatics;Nov2010, Vol. 26 Issue 22, p2833 

    Motivation: Membrane proteins (MPs) are important drug targets but knowledge of their exact structure is limited to relatively few examples. Existing homology-based structure prediction methods are designed for globular, water-soluble proteins. However, we are now beginning to have enough MP...

  • A protein sequence that can encode native structure by disfavoring alternate conformations. Wigley, W. Christian; Corboy, Michael J.; Cutler, Todd D.; Thibodeau, Patrick H.; Oldan, Jorge; Lee, Min Goo; Rizo, Josep; Hunt, John F.; Thomas, Philip J. // Nature Structural Biology;May2002, Vol. 9 Issue 5, p381 

    The linear sequence of amino acids contains all the necessary information for a protein to fold into its unique three-dimensional structure. Native protein sequences are known to accomplish this by promoting the formation of stable, kinetically accessible structures. Here we describe a Pro...

  • MemBrain: Improving the Accuracy of Predicting Transmembrane Helices. Hongbin Shen; Chou, James J. // PLoS ONE;2008, Vol. 3 Issue 6, p1 

    Prediction of transmembrane helices (TMH) in a helical membrane proteins provides valuable information about the protein topology when the high resolution structures are not available. Many predictors have been developed based on either amino acid hydrophobicity scale or pure statistical...

  • Organ targeting in vivo using phage display peptide libraries. Pasqualini, Renata; Ruoslahti, Erkki // Nature;3/28/1996, Vol. 380 Issue 6572, p364 

    Introduces a new approach to studying organ-selective targeting based on in vivo screening of random peptide sequences. The use of injected phage to select peptides that home to the brain; Tumor cells and leukocytes; Peptide sequences representing the first step towards identifying selective...

  • Supplementary Information S2.  // International Journal of Molecular Sciences;May2014, Vol. 15 Issue 5, pS1 

    The article lists protein sequences of hydroxylysine peptide fragments and non-hydroxylysine peptide fragments along with their identification number listed in a protein database UniProt.

  • Supplementary Information S4.  // International Journal of Molecular Sciences;May2014, Vol. 15 Issue 5, pS1 

    The article lists protein sequences of hydroxylysine peptide fragments and non-hydroxylysine peptide fragments along with their identification number listed in a protein database UniProt.

  • Prediction of the translocon-mediated membrane insertion free energies of protein sequences. Yungki Park; Volkhard Helms // Bioinformatics;May2008, Vol. 24 Issue 10, p1271 

    Motivation: Helical membrane proteins (HMPs) play crucial roles in a variety of cellular processes. Unlike water-soluble proteins, HMPs need not only to fold but also get inserted into the membrane to be fully functional. This process of membrane insertion is mediated by the translocon complex....

  • Domain Organization of Long Signal Peptides of Single-Pass Integral Membrane Proteins Reveals Multiple Functional Capacity. Hiss, Jan A.; Resch, Eduard; Schreiner, Alexander; Meissner, Michael; Starzinski-Powitz, Anna; Schneider, Gisbert // PLoS ONE;2008, Vol. 3 Issue 7, p1 

    Targeting signals direct proteins to their extra - or intracellular destination such as the plasma membrane or cellular organelles. Here we investigated the structure and function of exceptionally long signal peptides encompassing at least 40 amino acid residues. We discovered a two-domain...

  • Purification and characterization of cathepsin S from hepatopancreas of carp Cyprinus carpio. Pangkey, Henneke; Hara, Keniji; Tachibana, Katsuyasu; Min-Jie Cao; Osatomi, Kiyoshi; Ishihara, Tadashi // Fisheries Science;Dec2000, Vol. 66 Issue 6, p1130 

    Cathepsin S was purified from carp hepatopancreas to homogeneity up to 300-fold. The amino acid sequence of its NH2-terminus was determined to be V-P-D-A-M-D-W-Y-N-K-G-Y-V-T- D-V-K-N-Q. On the contrary, that of purified cathepsin L from carp hepatopancreas was to be V-P-N- S-L-D-W-R-E-K-G....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics