Re: NANOMED: [was Weekend tidbits~ Nanogirl News.]

Robert J. Bradbury (bradbury@www.aeiveos.com)
Mon, 6 Sep 1999 12:02:16 -0700 (PDT)

On Mon, 6 Sep 1999 hal@finney.org wrote:

>
> One note, from
> http://www.portlandpress.co.uk/books/isbn/1855781212.htm, is that 95%
> of the cell's lipid membranes are found internally, separating cellular
> compartments (mitochondria and other organelles, endoplasmic reticulum,
> the nucleus, etc.).

Quite possibly.

> So whatever method is used to pass through lipid membranes would be
> needed even more within the cell than for getting inside.

The cell goes to fairly complex lengths to not have to do this. The proteins that are targeted to the endoplasmic reticulum and everything downstream from that (golgi apparatus, peroxisomes (probably), outer cell membrane), are actually synthesized *into* the ER. So you don't have this

synthesize, fold, unfold, transport, refold, deliver process.
Instead it is synthesize while transporting, fold, deliver.

In contrast, I think all proteins that end up in the nucleus are synthesized, folded, then delivered. Their import into the nucleus is mediated by the nuclear pore complex (which is probably a real example of a "gatekeeper"). I've never read anything that indicates proteins are unfolded to get through the complex and I'm under the impression that really large proteins can't get into the nucleus. This mechanism is what makes me think there is a limit on the size of a viral DNA genome that can get transported into the nucleus. In theory you could feed the DNA through the pore as a thread but this seems like a *very* complex operation.

The interesting part is that all of these proteins have "targeting sequences" for the nucleus, peroxisomes, ER, mitochondria, etc. to get them to go to the right place with a minimum requirement for refolding. Transport is a *big* part of what higher cells have to manage.

Another interesting part of the whole cell structure is -- how does the nuclear pore mediate the transport of newly synthesized proteins or activated transcription factors *into* the nucleus and "old" grungy proteins or newly synthesized mRNA *out-of* the nucleus. What functions as the transport stop-lights?

Magic biology, (oh, nooooooo)...

Robert