| Autor: |
Zaigraev MM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 119997 Moscow, Russia.; Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Institutskiy per. 9, 141701 Moscow, Russia., Lyukmanova EN; Faculty of Biology, MSU-BIT Shenzhen University, Shenzhen 518172, China.; Interdisciplinary Scientific and Educational School of Moscow University 'Molecular Technologies of the Living Systems and Synthetic Biology', Biological Faculty, Lomonosov Moscow State University, Leninskie Gory, 119234 Moscow, Russia., Paramonov AS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 119997 Moscow, Russia., Shenkarev ZO; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 119997 Moscow, Russia.; Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Institutskiy per. 9, 141701 Moscow, Russia., Chugunov AO; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str. 16/10, 119997 Moscow, Russia.; Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Institutskiy per. 9, 141701 Moscow, Russia.; International Laboratory for Supercomputer Atomistic Modelling and Multi-Scale Analysis, National Research University Higher School of Economics, Myasnitskaya str. 20, 101000 Moscow, Russia. |
| Abstrakt: |
Ly6/uPAR proteins regulate many essential functions in the nervous and immune systems and epithelium. Most of these proteins contain single β-structural LU domains with three protruding loops and are glycosylphosphatidylinositol (GPI)-anchored to a membrane. The GPI-anchor role is currently poorly studied. Here, we investigated the positional and orientational preferences of six GPI-anchored proteins in the receptor-unbound state by molecular dynamics simulations. Regardless of the linker length between the LU domain and GPI-anchor, the proteins interacted with the membrane by polypeptide parts and N-/O-glycans. Lynx1, Lynx2, Lypd6B, and Ly6H contacted the membrane by the loop regions responsible for interactions with nicotinic acetylcholine receptors, while Lypd6 and CD59 demonstrated unique orientations with accessible receptor-binding sites. Thus, GPI-anchoring does not guarantee an optimal 'pre-orientation' of the LU domain for the receptor interaction. |
