Journal
BIOCHEMISTRY
Volume 45, Issue 25, Pages 7693-7699Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi060652l
Keywords
-
Categories
Funding
- NIGMS NIH HHS [R01 GM066009-01A1, R01 GM066009-03, R01 GM066009-05, R01 GM066009-01A1S1, GM066009, R01 GM066009-02, R01 GM066009, R01 GM066009-04] Funding Source: Medline
Ask authors/readers for more resources
Long-range intraprotein interactions give rise to many important protein behaviors. Understanding how energy is transduced through protein structures to either transmit a signal or elicit conformational changes is therefore a current challenge in structural biology. In an effort to understand such linkages, multiple V -> A mutations were made in the small globular protein eglin c. The physical responses, as mapped by NMR spin relaxation, residual dipolar couplings (RDCs), and scalar couplings, illustrate that the interior of this nonallosteric protein forms a dynamic network and that local perturbations are transmitted as dynamic and structural changes to distal sites as far as 16 angstrom away. Two basic types of propagation responses were observed: contiguous pathways of enhanced (attenuated) dynamics with no change in structure; and dispersed (noncontiguous) changes in methyl rotation rates that appear to result from subtle deformation of backbone structure. In addition, energy transmission is found to be unidirectional. In one mutant, an allosteric conformational change of a side chain is seen in the context of a pathway of propagated changes in picosecond to nanosecond dynamics. The observation of so many long-range interactions in a small, rigid system lends experimental weight to the idea that all well-folded proteins inherently possess allosteric features [Gunasekaran et al. (2004) Proteins 57, 433-443], and that dynamics are a rich source of information for mapping and gaining mechanistic insight into communication pathways in individual proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available