N-Terminal Domains in Two-Domain Proteins Are Biased to Be Shorter and Predicted to Fold Faster Than Their C-Terminal Counterparts

Etai Jacob, Ron Unger, Amnon Horovitz

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)1051-1056
Number of pages6
JournalCell Reports
Volume3
Issue number4
DOIs
StatePublished - 25 Apr 2013

Bibliographical note

Funding Information:
We thank Ariel Azia for helpful discussions and Kobi Zavaro for help with the graphics. This work was supported by the Kimmelman Center for Macromolecular Assembly. A.H. is an incumbent of the Carl and Dorothy Bennett Professorial Chair in Biochemistry.

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