Conformational Memory of a Protein Revealed by Single-Molecule Spectroscopy

Abstract

Proteins are supramolecular machines that carry out a wide range of different functions, many of which require flexibility. Up until now spontaneous conformational fluctuations of proteins have always been assumed to reflect a stochastic random process. However, if changing between different conformational states was random, then it would be difficult to understand how conformational control of protein function could have evolved. Here we demonstrate that a single protein can show conformational memory. This is exactly the process that can facilitate the evolution of control of switching between two conformational states that can then be used to regulate protein function.

Conformational memory in the association of the transmembrane protein phospholamban with the sarcoplasmic reticulum calcium pump SERCA

“…PLN regulates SERCA by altering the transition between the E2 and E1 conformational states, which manifests as a decrease in SERCA's calcium affinity. Herein, our data are consistent with conformational memory (36) in the SERCA-PLN regulatory complex. The SERCA-PLN complex attains distinct structural states depending on substrate conditions (Fig.…”

“…Moreover, once a particular SERCA-PLN inhibitory interaction was established, it persisted during continuous catalytic turnover of SERCA. This "conformational memory" (36) in the SERCA-PLN regulatory complex provides insights into the functional relevance of the published crystal structures of SERCA bound to PLN (11) and SLN (9,10).…”

From isolated light-harvesting complexes to the thylakoid membrane: a single-molecule perspective

“…The authors in the latter study further argue that conformational memory, in contrast to purely stochastic conformational switching, is a precondition for functional control of native light-harvesting [41].…”

Stability and properties of quasi-stable conformational states in the LH2 light-harvesting complex of Rbl. acidophilus bacteria formed by hexacoordination of bacteriochlorophyll a magnesium atom

“…In a later study of the LH2 complexes in a polymer film it was found that the same pigment-protein supramolecule can have different number (namely, 80 two, three or four) of conformational states [44,45].…”

“…For the LH2 complex of Rps.acidophila, considering its C 9 symmetry, the number of structurally different and symmetrically non-equivalent metastable conformations is 59[77], including 1 singly ligated and 4 doubly ligated. The actual number of such conformations is unknown, and the number assumed theoretically to account for experimental data on spectroscopic shifts and fluorescence intermittency greatly varies: two to four per each BCL in B850 ring[14], two per BCL[42,43], two or three per complex [15] and up to four per complex[44].Two motions are needed for the formaton of metastable conformational state of the LH2 complex: an acetyl group rotation associated with a hydrogen bond break and a shift of a BCL molecule towards a neighboring one. According to our MD results, these two motions occur at significantly different rates, BCL…”