Abstract:
:Repeat proteins contain short, tandem arrays of simple structural motifs (20-40 aa). These stack together to form nonglobular structures that are stabilized by short-range interactions from residues close in primary sequence. Unlike globular proteins, they have few, if any, long-range nonlocal stabilizing interactions. One ubiquitous repeat is the tetratricopeptide motif (TPR), a 34-aa helix-turn-helix motif. In this article we describe the folding kinetics of a series of 7 designed TPR proteins that are assembled from arraying identical designed consensus repeats (CTPRan). These range from the smallest 2-repeat protein to a large 10-repeat protein (approximately 350 aa). In particular, we describe how the energy landscape changes with the addition of repeat units. The data reveal that although the CTPRa proteins have low local frustration, their highly symmetric, modular native structure is reflected in their multistate kinetics of unfolding and folding. Moreover, although the initial folding of all CTPRan proteins involves a nucleus with similar solvent accessibility, their subsequent folding to the native structure depends directly on repeat number. This corresponds to an increasingly complex landscape that culminates in CTPRa10 populating a misfolded, off-pathway intermediate. These results extend our current understanding of the malleable folding pathways of repeat proteins and highlight the consequences of adding identical repeats to the energy landscape.
journal_name
Proc Natl Acad Sci U S Aauthors
Javadi Y,Main ERdoi
10.1073/pnas.0907455106subject
Has Abstractpub_date
2009-10-13 00:00:00pages
17383-8issue
41eissn
0027-8424issn
1091-6490pii
0907455106journal_volume
106pub_type
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