Folding of a LysM domain: Entropy-enthalpy compensation in the transition state of an ideal two-state folder

JOURNAL OF MOLECULAR BIOLOGY

卷:380

Article

Nickson, Adrian A.¹  Stoll, Kate E.¹  Clarke, Jane¹ 

[1] Univ Cambridge, Dept Chem, MRC Ctr Prot Engn, Cambridge CB2 1EW, England

关键词: protein folding;    phi-value;    foldon;    Eyring plot;    entropy-enthalpy balance;   

DOI  :  10.1016/j.jmb.2008.05.020

来源: Elsevier

【 摘 要 】

Protein-engineering methods (Phi-values) were used to investigate the folding transition state of a lysin motif (LysM) domain from Escherichia coli membrane-bound lytic murein transglycosylase D. This domain consists of just 48 structured residues in a symmetrical arrangement and is the smallest a[ protein yet investigated using these methods. An extensive mutational analysis revealed a highly robust folding pathway with no detectable transition state plasticity, indicating that LysM is an example of an ideal two-state folder. The pattern of Phi-values denotes a highly polarised transition state, with significant formation of the helices but no structure within the beta-sheet. Remarkably, this transition state remains polarised after circularisation of the domain, and exhibits an identical Phi-value pattern; however, the interactions within the transition state are uniformly weaker in the circular variant. This observation is supported by results from an Eyring analysis of the folding rates of the two proteins. We propose that the folding pathway of LysM is dominated by enthalpic rather than entropic considerations, and suggest that the lower entropy cost of formation of the circular transition state is balanced, to some extent, by the lower enthalpy of contacts within this structure. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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