| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
2 Celera Genomics, Rockville, Maryland 20850, USA
Reprint requests to: Dr. Jonathan King, Department of Biology, Massachusetts Institute of Technology, Room 68-330, Cambridge, MA 02139, USA; e-mail: jaking{at}mit.edu; fax: (617) 252-1843.
Patterns of hydrophobic and hydrophilic residues play a major role in protein folding and function. Long, predominantly hydrophobic strings of 20–22 amino acids each are associated with transmembrane helices and have been used to identify such sequences. Much less attention has been paid to hydrophobic sequences within globular proteins. In prior work on computer simulations of the competition between on-pathway folding and off-pathway aggregate formation, we found that long sequences of consecutive hydrophobic residues promoted aggregation within the model, even controlling for overall hydrophobic content. We report here on an analysis of the frequencies of different lengths of contiguous blocks of hydrophobic residues in a database of amino acid sequences of proteins of known structure. Sequences of three or more consecutive hydrophobic residues are found to be significantly less common in actual globular proteins than would be predicted if residues were selected independently. The result may reflect selection against long blocks of hydrophobic residues within globular proteins relative to what would be expected if residue hydrophobicities were independent of those of nearby residues in the sequence.
Keywords: Sequence database; bioinformatics; aggregation; inclusion body; hydrophobic residues
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Monsellier, M. Ramazzotti, P. P. de Laureto, G.-G. Tartaglia, N. Taddei, A. Fontana, M. Vendruscolo, and F. Chiti The Distribution of Residues in a Polypeptide Sequence Is a Determinant of Aggregation Optimized by Evolution Biophys. J., December 15, 2007; 93(12): 4382 - 4391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Stefani Generic Cell Dysfunction in Neurodegenerative Disorders: Role of Surfaces in Early Protein Misfolding, Aggregation, and Aggregate Cytotoxicity Neuroscientist, October 1, 2007; 13(5): 519 - 531. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Schwartz and J. King Frequencies of hydrophobic and hydrophilic runs and alternations in proteins of known structure Protein Sci., January 1, 2006; 15(1): 102 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Fawzi, V. Chubukov, L. A. Clark, S. Brown, and T. Head-Gordon Influence of denatured and intermediate states of folding on protein aggregation Protein Sci., April 1, 2005; 14(4): 993 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ventura, J. Zurdo, S. Narayanan, M. Parreno, R. Mangues, B. Reif, F. Chiti, E. Giannoni, C. M. Dobson, F. X. Aviles, et al. Short amino acid stretches can mediate amyloid formation in globular proteins: The Src homology 3 (SH3) case PNAS, May 11, 2004; 101(19): 7258 - 7263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lopez de la Paz and L. Serrano Sequence determinants of amyloid fibril formation PNAS, January 6, 2004; 101(1): 87 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Sim and T. P. Creamer Abundance and Distributions of Eukaryote Protein Simple Sequences Mol. Cell. Proteomics, December 1, 2002; 1(12): 983 - 995. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
