title: Rigidity of transmembrane proteins determines their cluster shape.
abstract: Protein aggregation in cell membrane is vital for the majority of biological functions. Recent experimental results suggest that transmembrane domains of proteins such as α-helices and β-sheets have different structural rigidities. We use molecular dynamics simulation of a coarse-grained model of protein-embedded lipid membranes to investigate the mechanisms of protein clustering. For a variety of protein concentrations, our simulations under thermal equilibrium conditions reveal that the structural rigidity of transmembrane domains dramatically affects interactions and changes the shape of the cluster. We have observed stable large aggregates even in the absence of hydrophobic mismatch, which has been previously proposed as the mechanism of protein aggregation. According to our results, semiflexible proteins aggregate to form two-dimensional clusters, while rigid proteins, by contrast, form one-dimensional string-like structures. By assuming two probable scenarios for the formation of a two-dimensional triangular structure, we calculate the lipid density around protein clusters and find that the difference in lipid distribution around rigid and semiflexible proteins determines the one- or two-dimensional nature of aggregates. It is found that lipids move faster around semiflexible proteins than rigid ones. The aggregation mechanism suggested in this paper can be tested by current state-of-the-art experimental facilities.
authors: Department of Mechanical Engineering, Sharif University of Technology, P.O. Box 11155-9567, Tehran, Iran.
authors: Hamidreza
authors: H
authors: Jafarinia
authors: Reservoir Engineering Research Institute, Palo Alto, California 94301, USA.
authors: Atefeh
authors: A
authors: Khoshnood
authors: Department of Astronomy, University of California, Berkeley, California 94720, USA.
authors: Mir Abbas
authors: MA
authors: Jalali
mesh_terms: D004058:Diffusion; D004548:Elasticity; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009038:Motion; D011487:Protein Conformation; D055503:Protein Multimerization; D013995:Time; D014618:Vacuum
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins