title: N-terminal domains in two-domain proteins are biased to be shorter and predicted to fold faster than their C-terminal counterparts.
abstract: Computational analysis of proteomes in all kingdoms of life reveals a strong tendency for N-terminal domains in two-domain proteins to have shorter sequences than their neighboring C-terminal domains. Given that folding rates are affected by chain length, we asked whether the tendency for N-terminal domains to be shorter than their neighboring C-terminal domains reflects selection for faster-folding N-terminal domains. Calculations of absolute contact order, another predictor of folding rate, provide additional evidence that N-terminal domains tend to fold faster than their neighboring C-terminal domains. A possible explanation for this bias, which is more pronounced in prokaryotes than in eukaryotes, is that faster folding of N-terminal domains reduces the risk for protein aggregation during folding by preventing formation of nonnative interdomain interactions. This explanation is supported by our finding that two-domain proteins with a shorter N-terminal domain are much more abundant than those with a shorter C-terminal domain.
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Etai
authors.initials: E
authors.lastname: Jacob
authors.forename: Ron
authors.initials: R
authors.lastname: Unger
authors.forename: Amnon
authors.initials: A
authors.lastname: Horovitz
mesh_terms: D000818:Animals; D030562:Databases, Protein; D056890:Eukaryota / Q000378:metabolism; D006801:Humans; D011387:Prokaryotic Cells / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins