An Electrostatic Charge Partitioning Model for the Dissociation of Protein Complexes in the Gas Phase |
| |
Authors: | Stephen V Sciuto Jiangjiang Liu Lars Konermann |
| |
Institution: | (1) Department of Chemistry, The University of Western Ontario, London, Ontario, N6A 5B7, Canada; |
| |
Abstract: | Electrosprayed multi-protein complexes can be dissociated by collisional activation in the gas phase. Typically, these processes
follow a mechanism whereby a single subunit gets ejected with a disproportionately high amount of charge relative to its mass.
This asymmetric behavior suggests that the departing subunit undergoes some degree of unfolding prior to being separated from
the residual complex. These structural changes occur concomitantly with charge (proton) transfer towards the subunit that
is being unraveled. Charge accumulation takes place up to the point where the subunit loses physical contact with the residual
complex. This work develops a simple electrostatic model for studying the relationship between conformational changes and
charge enrichment during collisional activation. Folded subunits are described as spheres that carry continuum surface charge.
The unfolded chain is envisioned as random coil bead string. Simulations are guided by the principle that the system will
adopt the charge configuration with the lowest potential energy for any backbone conformation. A finite-difference gradient
algorithm is used to determine the charge on each subunit throughout the dissociation process. Both dimeric and tetrameric
protein complexes are investigated. The model reproduces the occurrence of asymmetric charge partitioning for dissociation
events that are preceded by subunit unfolding. Quantitative comparisons of experimental MS/MS data with model predictions
yield estimates of the structural changes that occur during collisional activation. Our findings suggest that subunit separation
can occur over a wide range of scission point structures that correspond to different degrees of unfolding. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|