Hydration Dynamics of a Peripheral Membrane Protein

Abstract

Water dynamics in the hydration shell of the peripheral membrane protein annexin B12 were studied using MD simulations and Overhauser DNP-enhanced NMR. We show that retardation of water motions near phospholipid bilayers is extended by the presence of a membrane-bound protein, up to around 10 Å above that protein. Near the membrane surface, electrostatic interactions with the lipid head groups strongly slow down water dynamics, whereas protein-induced water retardation is weaker and dominates only at distances beyond 10 Å from the membrane surface. The results can be understood from a simple model based on additive contributions from the membrane and the protein to the activation free energy barriers of water diffusion next to the biomolecular surfaces. Furthermore, analysis of the intermolecular vibrations of the water network reveals that retarded water motions near the membrane shift the vibrational modes to higher frequencies, which we used to identify an entropy gradient from the membrane surface towards the bulk water. Our results have implications for processes that take place at lipid membrane surfaces, including molecular recognition, binding, and protein-protein interactions.

Spatially Heterogeneous Surface Water Diffusivity around Structured Protein Surfaces at Equilibrium

“…This is motivated by the observation that local hydration water dynamics is only partially determined by the experimentally labeled site itself, and to a larger degree by its more extended chemical environment. This is suggested, for example, by a previous comparison between simulations of the unlabeled annexin protein with ODNP experiments that are comparable to the ones reported here 19 . To test for the potential impact of local modifications, we carried out an additional set of simulations for the 5-residue peptides that included the cysteine mutation.…”

“…We analyzed the DW on a range of surfaces that can be separated into two categories: ones that take part in highly specific binding, such as folded globular proteins, and ones that tend to take part in less specific binding, such as intrinsically disordered proteins (IDPs), small peptides, and liposomes. Here, we analyzed the DW retardation on the folded globular protein surfaces of Annexin XII (Anx) 19 and CheY, the intrinsically disordered proteins of α-Synuclein (α-Syn) 18 and ΔTau187 17 , CheY-inspired 5-residue peptides, poly proline peptides with systematically varied charges (discussed in SI), and model LUV liposome surfaces made of DPPC and DOPC 20 . The description for each system is found in Methods.…”

“…In this report we present and compare ODNP measurements on the surface of ΔTau-187 17 , α-synuclein 18 , Annexin XII 19 , and DOPC/DPPC LUV liposomes 20 . The hydration dynamics on the surface of ΔTau-187 monomers were measured on sites 313, 316, 322, 400, and 404 17 , of α-synuclein measured at sites 77, 81, 85, 86, 90, 93, 95, 98, 100, 101, 124, and 136 18 , and of Annexin XII measured at sites 12, 16, 104, 112, 121, 124, 137, 141, 162, 180, and 260 XII 19 .…”

How Ligand Binding Affects the Dynamical Transition Temperature in Proteins

“…Additionally, the coupling of the dynamics of water molecules with proteins has been proposed to decrease the motion of waters residing at the surface . Similar conclusions have been made for water molecules in the vicinity of a membrane environment, where their dynamics are slowed remarkably compared to when in bulk solvent …”

Identifying Protein Conformational Dynamics Using Spin‐label ESR

“…[76][77][78][79][80][81] However, the experimental analysiso fl ocal water dynamics is very difficult as the bulk and surface, or internal water dynamics often do not have distinct spectroscopic signatures. Recently,E SR techniques as well as ESR-related DNP techniques [82,83] have been enhanced to identify dynamical components underlying the protein-water interactions.…”