Are structural biases at protein termini a signature of vectorial folding?

Experimental investigations of the biosynthesis of a number of proteins have pointed out that part of the native structure may be acquired already during translation. We carried out a comprehensive statistical analysis of some average structural properties of proteins that have been put forward as possible signatures of this progressive buildup process. Contrary to a widespread belief, we found that there is no major propensity of the amino acids to form contacts with residues that are closer to the N-terminus. Moreover, we found that the C-terminus is significantly more compact and locally organized than the N-terminus. This bias, though, is unlikely to be related to vectorial effects, since it correlates with subtle differences in the primary sequence. These findings indicate that even if proteins acquire their structure vectorially, no signature of this seems to be detectable in their average structural properties. 2005 Wiley-Liss, Inc.