Molecular Modeling and Simulation of Human Stomatin and Predictions

for its Membrane Association

Stomatin is a membrane protein in human red blood cells. The crystal structure, in which the monomeric stomatin from the hyperthermophilic archaeon Pyrococcus horikoshii consists of the α/β domain and the C-terminal α-helical segment, forms a homo-trimer, and stomatin is organized into further high order homo-oligomeric complexes, comprising 9- to 12-mers. To better understand the molecular functions of stomatin, the hypothesis how human stomatin oligomerizes and is associated with cell membranes should be validated. Here, we report what conformations can be generated from the stomatin structure by estimating the flexibility of α-helical segments of human stomatin. And we also simulate how the oligomeric structure of human stomatin interacts with cell membranes. The results showed that the α-helical segments can make flexible movements; the α-helical segment and the α/β domain of the monomer can form a flat structure, and the α-helical segments of the trimer can approach lipid membranes. Based on the flat structure of human stomatin, we proposed a hypothetical oligomeric model to interact with the surface of cell membranes. The oligomeric model well explains the stomatin functions as a scaffolding protein to support the cell membrane.

Нe obtained model of human stomatin consists of the α/β domain and the α-helical segment. Нe α/β domain and α-helical segment is estimated to be located on cell membranes in cytosol. Although the modeled structure does not have N-terminal and C-terminal regions of human stomatin, the N-terminal region is predicted to have transmembrane regions, and the C-terminal region is essential to oligomerize stomatins. Appropriate template structures of the Nterminal and C-terminal regions of human stomatin did not exist because the template structures of the terminal regions have larger evalues compared with ph stomatin and mouse stomatin. It is possible to be a bad accuracy in predicting the terminal regions, even if we used the template structures. In addition, terminal regions of proteins are oÑ–en disordered. It would be diÙ¹cult to build the terminal regions of human stomatin. Нe results of the Ramachandran plot and Verify Protein (Figure 2) suggest that the modeled structure is accurate to a certain extent. However, some residues in the modeled structure have low verify scores. Residues with low verify scores show that there are hydrophobic patches on the surface of the structure. Нe result suggests that the hydrophobic patches of human stomatin are responsible for binding to lipid membranes.

Authors can submit manuscripts online at Editorial Tracking System (https://www.longdom.org/submissions/data-mining-genomics-proteomics.html) or forwarded to the Editorial Office at: proteomdataming@oajournal.org 

 Benefits of Publication with us:

• Fast track Peer-review process in 21 days.
• Publication immediately after acceptance.
• Peer-review by international experts.
• Enhanced visibility for the published articles through digital media & Open-Access.

Media Contact:
Alex John 
Managing Editor
Journal of Data mining in Genomics and Proteomics
Email: proteomdataming@oajournal.org