Negative charge is a criteria for the selective passage of particles through the nuclear Pore to enter the NUCLEUS--yet ANOTHER study
Negative Charge IS the NLS (nuclear localization signal)
Charge as a Selection Criterion for Translocation through the Nuclear Pore Complex
Colwell, Lucy J et al. “Charge as a selection criterion for translocation through the nuclear pore complex.” PLoS computational biology vol. 6,4 e1000747. 22 Apr. 2010, doi:10.1371/journal.pcbi.1000747
(we are going to skip a bunch, unless you want to read the study—go for it. We are focusing AGAIN on negatively charged particles being driven into the nucleus through the nuclear pore.)
”Our study finds that transport receptors are more negatively charged than the majority of cellular proteins. Existing crystal structures of transport receptors such as importinβ reveal that negative charge is distributed over the surface of the protein (Fig. S4; [40], [45]). High sequence homology of importinβ-like transport receptors, both within species and between species, suggests that net negative surface charge is a conserved property of this protein family.
How could negative surface charge promote the translocation of transport receptors through the NPC channel? Current models of translocation through the NPC postulate that hydrophobic FG-repeats within the selective barrier principally determine NPC selectivity [6], [12], [32], [36], [39], [48], [54], [55]. We suggest that charge within the NPC channel may be a second feature relevant for translocation. The unfolded domains that separate FG-repeats are characterized by net positive charge (Fig. 2C, D), and we suggest that they represent a critical element of the selective barrier. Indeed, the positive charge of the spacers is conserved across multiple species [56], suggesting a functional constraint on the design of the spacer elements.
We propose that their negative surface charge allows transport receptors to adsorb to the positively charged nucleoporin domains via electrostatic interactions, facilitating selective partitioning of transport receptors and transport receptor-cargo complexes into the NPC (Fig. 4). Those soluble cellular proteins that are positively charged (Fig. 1B, C) should fail to enter the NPC efficiently because the corresponding energy barrier is too high. Note that according to this model, a translocating particle could become trapped within the NPC if its charge is too negative. The translocation rate is maximal only if the charge of a particle compensates for the decrease in entropy, rendering the total free energy barrier flat. We also note that repulsive electrostatic interactions between the patches of positive charge on the FG-domains may compete with the meshwork forming inter-FG linkages.”
Breakdown:
The unfolded domains separating FG-repeats are characterized by a net positive charge. The main thing to think about, is the nucleus has pores in it, or holes. And there are areas with positive charges and negative charges. The negatively charged particles LIKE the positively charged areas, and are attracted to it.
So we have THREE parts of the nucleus now, with the last study mentioning the residue, but also we have the positively charged chromatin, and now, these repeats.
(don’t let anyone dissuade from what is happening here, regardless of laurels, or twitter status)
The researchers propose that this positive charge, along with the negative charge of transport receptors, facilitates electrostatic interactions that aid in the selective partitioning of transport receptors and their cargo complexes into the NPC.
All you have to really take away here is once again, negatively charged things are going into the nucleus, as long as they fit in there.
But let’s go bonkers with it:
The negative surface charge of transport receptors allows them to adhere to the positively charged nucleoporin domains within the NPC via electrostatic interactions. This selective partitioning mechanism means cellular proteins with a positive charge may struggle to efficiently enter the NPC due to the high energy barrier associated with their interaction with the NPC components. The translocation rate through the NPC is maximal when the charge of a particle compensates for the decrease in entropy, resulting in a total free energy barrier that is flat. However, particles with an excessively negative charge may become trapped within the NPC, indicating a balance in charge interactions. There is a possibility of repulsive electrostatic interactions between patches of positive charge on the FG-domains within the NPC, which may compete with the meshwork forming inter-FG linkages.
feck twitter