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Membrane fusion processes are mediated and regulated by a growing family of soluble and integral membrane proteins termed fusion proteins.
Diverse membrane fusion processes occur in cells through a common set of steps: membrane tethering, docking, and fusion (Brocker et al., 2010; Li and Chin, 2003).
Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes.
In further support of the notion that ether lipids facilitate membrane fusion processes, ether lipid deficiency disrupts the integrity of the blood-testis barrier by affecting the sorting, endocytosis, and recycling of tight junction proteins (Komljenovic et al., 2009).
Previous works (Zhao et al. 2015; Zhou et al. 2015) showed that human 20S particle functioning in membrane fusion processes in eukaryotic cells is composed of two parts relatively flexible to each other: the SS complex with pseudo four-fold symmetry and the hexameric NSF complex.
Tethering factors for many intracellular membrane fusion processes have been identified and shown to not only act as physical bridges to connect two opposing membranes but also interact with multiple components of the fusion machinery to promote docking and SNARE-mediated membrane fusion (Brocker et al., 2010; Yu and Hughson, 2010).
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However, the exact conformations that manifest in the membrane fusion process are still not clear.
When the membrane fusion process initiates, gp120 interacts with CD4 molecule on the surface of target cells with a high affinity, which facilitates a series of conformational changes.
The native conformation of MPER, or the conformation capable of inducing neutralizing antibodies, has not been determined, and the change of MPER conformation during the membrane fusion process also has not been elucidated.
However, researchers have not yet determined the exact structure of gp41, the native conformation of MPER, or the conformation of MPER capable of inducing neutralizing antibodies, let alone the allosteric mode of gp41, especially MPER during the membrane fusion process.
The chimeric peptide offers the advantage of targeting two gp41 regions simultaneously: the fusion peptide and the loop both of which are membrane active and participate in the membrane fusion process.
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