The denatured state dictates the topology of two proteins with almost identical sequence but different native structure and function.

Abstract : The protein folding problem is often studied by comparing the mechanisms of proteins sharing the same structure but different sequence. The recent design of the two proteins G(A)88 and G(B)88, displaying different structures and functions while sharing 88% sequence identity (49 out of 56 amino acids), allows the unique opportunity for a complementary approach. At which stage of its folding pathway does a protein commit to a given topology? Which residues are crucial in directing folding mechanisms to a given structure? By using a combination of biophysical and computational techniques, we have characterized the folding of both G(A)88 and G(B)88. We show that, contrary to expectation, G(B)88, characterized by a native α+β fold, displays in the denatured state a content of native-like helical structure greater than G(A)88, which is all-α in its native state. Both experiments and simulations indicate that such residual structure may be tuned by changing pH. Thus, despite the high sequence identity, the folding pathways for these two proteins appear to diverge as early as in the denatured state. Our results suggest a mechanism whereby protein topology is committed very early along the folding pathway, being imprinted in the residual structure of the denatured state.
Document type :
Journal articles
Complete list of metadatas

Cited literature [37 references]  Display  Hide  Download

https://hal-riip.archives-ouvertes.fr/pasteur-00982071
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti <>
Submitted on : Wednesday, April 23, 2014 - 11:32:37 AM
Last modification on : Tuesday, April 30, 2019 - 2:34:02 PM
Long-term archiving on : Monday, April 10, 2017 - 4:39:45 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Angela Morrone, Michelle E Mccully, Philip N Bryan, Maurizio Brunori, Valerie Daggett, et al.. The denatured state dictates the topology of two proteins with almost identical sequence but different native structure and function.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, 286 (5), pp.3863-72. ⟨10.1074/jbc.M110.155911⟩. ⟨pasteur-00982071⟩

Share

Metrics

Record views

78