3p63
Structure of M. laminosus Ferredoxin with a shorter L1,2 loop
Structural highlights
FunctionFER_MASLA Ferredoxins are iron-sulfur proteins that transfer electrons in a wide variety of metabolic reactions. Publication Abstract from PubMedRegulation of protein function via cracking, or local unfolding and refolding of substructures, is becoming a widely recognized mechanism of functional control. Oftentimes, cracking events are localized to secondary and tertiary structure interactions between domains that control the optimal position for catalysis and/or the formation of protein complexes. Small changes in free energy associated with ligand binding, phosphorylation, etc., can tip the balance and provide a regulatory functional switch. However, understanding the factors controlling function in single-domain proteins is still a significant challenge to structural biologists. We investigated the functional landscape of a single-domain plant-type ferredoxin protein and the effect of a distal loop on the electron-transfer center. We find the global stability and structure are minimally perturbed with mutation, whereas the functional properties are altered. Specifically, truncating the L1,2 loop does not lead to large-scale changes in the structure, determined via X-ray crystallography. Further, the overall thermal stability of the protein is only marginally perturbed by the mutation. However, even though the mutation is distal to the iron-sulfur cluster ( approximately 20 A), it leads to a significant change in the redox potential of the iron-sulfur cluster (57 mV). Structure-based all-atom simulations indicate correlated dynamical changes between the surface-exposed loop and the iron-sulfur cluster-binding region. Our results suggest intrinsic communication channels within the ferredoxin fold, composed of many short-range interactions, lead to the propagation of long-range signals. Accordingly, protein interface interactions that involve L1,2 could potentially signal functional changes in distal regions, similar to what is observed in other allosteric systems. Allostery in the ferredoxin protein motif does not involve a conformational switch.,Nechushtai R, Lammert H, Michaeli D, Eisenberg-Domovich Y, Zuris JA, Luca MA, Capraro DT, Fish A, Shimshon O, Roy M, Schug A, Whitford PC, Livnah O, Onuchic JN, Jennings PA Proc Natl Acad Sci U S A. 2011 Jan 25. PMID:21266547[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
