Race to the native state
Year: 2018
Type: article
Abstract: In contrast to other biopolymers such as RNA, most foldable protein sequences have a single, unique native structure, which is the most stable conformation. Understanding this remarkable property has been the long-held goal of protein folding research (1, 2). Once folded, proteins will undergo transitions between different conformational states within the native free-energy basin, often associated with their function; however, in most cases, these can be thought of as only local changes or deformations of structure that do not change the overall fold. On the other hand, a small number of proteins have been identified in which a more profound rearrangement of the fold can occur, with the most extreme examples being protein sequences that can switch to a completely different folded state as a function of environmental conditions or ligand binding (3). An example in which a subtle change of fold is used for functional regulation is found in the serine protease inhibitor family known as serpins. In this case, it appears that the initially formed “native” structure is not the thermodynamically most stable fold. In PNAS, Rao and Gosavi (4) investigate the origin of this kinetically controlled folding for a prototypical serpin, α1-antitrypsin.
Serpins are an abundant type of protease inhibitor, most commonly inhibiting chymotrypsin-like serine proteases (5) by a suicide mechanism: The protein initially folds to an active, inhibitory fold (Fig. 1, Top Left ) in which the exposed reactive center loop (RCL) serves as a recognition motif for proteases. Binding of the protease results in cleavage of the RCL loop and covalent linkage of the serpin to the protease. At the …
[↵][1]1Email: robert.best2{at}nih.gov.
[1]: #xref-corresp-1-1
Author: Robert B. Best
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2791259383