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(PNAS)   Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate   (pnas.org) divider line 258
    More: Obvious  
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14376 clicks; posted to Main » on 15 May 2007 at 7:02 PM   |  Favorite    |   share:  Share on Twitter share via Email Share on Facebook   more»



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2007-05-15 07:11:51 PM
PENIS!
 
2007-05-15 07:12:22 PM
I kept telling everybody that exact same thing, but nobody believed me.
 
2007-05-15 07:13:13 PM
If that is getting pimped on fark check out these from my sister.
main page http://www.pnas.org/cgi/content/full/103/38/14176
movies http://www.pnas.org/cgi/content/full/0604725103/DC1

basically my sister came up with a new way to study the toxins associated with Clostridium difficile.
 
2007-05-15 07:15:38 PM
Do you serve it with red or white wine?
 
2007-05-15 07:17:15 PM
Uhuhhuhuhuhuhuhuhuhuh...they said hydrophilic!
 
2007-05-15 07:17:29 PM
I remember enough about my college chemistry courses to know that they were talking about protiens from the headline... but that's about it!
 
2007-05-15 07:18:03 PM
Mad Scientist: I've published in PNAS, so I'm getting a kick out of these replies...

Your MAD!
 
2007-05-15 07:19:07 PM
So what... can I post my papers?

http://www.ingentaconnect.com/content/els/01413910/2003/00000082/^A/art0 0158

An old version, but nothing's changed much.
 
2007-05-15 07:19:20 PM
Who didn't know that? Why not the DUMBASS tag subby?
 
2007-05-15 07:19:20 PM
not ironic
 
2007-05-15 07:19:44 PM
That's what she said?

/got nuthin'
 
2007-05-15 07:20:27 PM
sounds like another paris hilton reference to me
 
2007-05-15 07:21:29 PM
Ha Ha
stk1841's sister has a yeast infection!
 
2007-05-15 07:21:49 PM
stk1841
basically my sister came up with a new way to study the toxins associated with Clostridium difficile.

Oh yeah? Well *I*...ummm...errr...ahhh...nanoparticles.

Never mind.
 
2007-05-15 07:22:25 PM
Um.. whatever he said.
 
2007-05-15 07:23:03 PM
Man, that is such BULLSHIAT.

/I blame Bush.
 
2007-05-15 07:23:46 PM
TTIWWP

c'mon intramembrane protease pix!!!
 
2007-05-15 07:24:00 PM
Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Sed scelerisque, ipsum id condimentum commodo, mauris erat volutpat nibh, nec lacinia pede justo feugiat arcu. Donec risus. Maecenas vestibulum purus sed quam. Pellentesque pellentesque felis id erat. Etiam tellus diam, sagittis at, rutrum ac, dignissim id, mi. Nullam iaculis purus in dolor. Proin porta eros in risus. Nam orci massa, ornare vel, scelerisque ut, accumsan eu, lectus. Nullam pharetra iaculis quam. Vestibulum adipiscing lacus quis ligula. Nunc non urna.
 
2007-05-15 07:24:10 PM
The terrorist win I guess.
 
2007-05-15 07:24:51 PM
WHAT??? I finally decide, after all these years of being annoyed, to hop on the "Russa does this to YOU" joke bandwagon, and fark filters them out?? :(
 
2007-05-15 07:25:04 PM
I like trains.
 
2007-05-15 07:26:04 PM
Nice to see some molecular biology on FARK for a change instead of all the weird crime crap.
 
2007-05-15 07:26:11 PM
....and you have meth.
 
2007-05-15 07:27:25 PM
I submitted this with a funnier headline...
 
2007-05-15 07:27:47 PM
But will it make my P3N15 B1@@3R?!?!
 
2007-05-15 07:28:04 PM
FTFA:
Intramembrane proteolysis is a core regulatory mechanism of cells that raises a biochemical paradox of how hydrolysis of peptide bonds is accomplished within the normally hydrophobic environment of the membrane. Recent high-resolution crystal structures have revealed that rhomboid proteases contain a catalytic serine recessed into the plane of the membrane, within a hydrophilic cavity that opens to the extracellular face, but protected laterally from membrane lipids by a ring of transmembrane segments. This architecture poses questions about how substrates enter the internal active site laterally from membrane lipid. Because structures are static glimpses of a dynamic enzyme, we have taken a structure-function approach analyzing >40 engineered variants to identify the gating mechanism used by rhomboid proteases. Importantly, our analyses were conducted with a substrate that we show is cleaved at two intramembrane sites within the previously defined Spitz substrate motif. Engineered mutants in the L1 loop and active-site region of the GlpG rhomboid protease suggest an important structural, rather than dynamic, gating function for the L1 loop that was first proposed to be the substrate gate. Conversely, three classes of mutations that promote transmembrane helix 5 displacement away from the protease core dramatically enhanced enzyme activity 4- to 10-fold. Our functional analyses have identified transmembrane helix 5 movement to gate lateral substrate entry as a rate-limiting step in intramembrane proteolysis. Moreover, our mutagenesis also underscores the importance of other residue interactions within the enzyme that warrant further scrutiny.

The Aristocrats!
 
2007-05-15 07:28:20 PM
Bravo submitter, excellent use of the obvious tag.
 
2007-05-15 07:28:23 PM
see i told you so - deep hole that is wet at the bottom = paris hilton
 
2007-05-15 07:31:06 PM
Sorry, but that's not a hair question.
 
2007-05-15 07:31:39 PM
I don't get it, what's the joke?

The name of the journal is PNAS, which could be read as Pee-NAS and that sounds a little like penis, which always makes me giggle. Is that the joke?
 
2007-05-15 07:35:26 PM
"This is blasphemy! This is enzymatic analysis of a rhomboid intramembrane protease!"

"Enzymatic analysis of a rhomboid intramembrane protease? This! Is! SPARTAAAAA!"

*kick*

/meh
 
2007-05-15 07:35:51 PM
So sad that our society values ignorance so highly.
 
2007-05-15 07:36:23 PM
does this have something to do with boobies?
 
2007-05-15 07:36:41 PM
Well, Du-uh.
Heck, even *I* know that.
How about applying that theory to single allele substitution, and how that can effect birth defects?
/get those renegade nucleotide nucleotides off my original DNA strand!
Upitty SNPs.
I mean snips.
 
2007-05-15 07:37:43 PM
What did you call me?!
 
2007-05-15 07:37:45 PM
Bowen: I don't get it, what's the joke?

The joke might be that many of us have no idea what's going on.
 
2007-05-15 07:37:48 PM
Too bad this isn't voting enabled, too.
 
zz9
2007-05-15 07:38:39 PM
They should have just put lipstick on the rhomboid intramembrane protease and see if it left a mark.
 
2007-05-15 07:38:42 PM
Thatguy: Man, that is such BULLSHIAT.

B-B-B-But Clinton!
 
2007-05-15 07:39:26 PM
Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate is correct, but I'm afraid you didn't answer in the form of a question.
 
2007-05-15 07:40:25 PM
i102.photobucket.com

Finkle knew about this way before you guys did. L'Chaim!
 
2007-05-15 07:40:39 PM
All the federal research dollars spent on NIH and NAS grants, makes one ask:

www.booksamillion.com
 
2007-05-15 07:40:45 PM
www.msu.edu
 
2007-05-15 07:41:00 PM
Call the NAACP!
 
2007-05-15 07:42:21 PM
Dude... wait, what?
 
2007-05-15 07:42:38 PM
1. Well DUH!

2. Rhomboids are found in virtually all organisms and were first discovered as proteases in 2001. Evidence for proteolytic function included conserved serine and histidine residues that were essential for activity in cells, sensitivity to certain serine protease inhibitors, and a cleavage site within the transmembrane (TM) region of the substrate. Bacterial expression and purification further demonstrated that rhomboids work alone, without the need for other protein factors. The recent crystal structures (all of bacterial rhomboid orthologs) have confirmed the six-TM helix topology of the protein and removed any doubt about their specific identity as serine proteases.

3. PNAS - huh huh huh huh huh
 
2007-05-15 07:43:02 PM
Best use of the Obvious tag ever.
 
2007-05-15 07:45:32 PM
But why should I care about Rhomboids ExcessNeckSkin?
So they cleave stuff in membranes, do they do anything else cool? Like activate any cell signaling pathways or something?
 
2007-05-15 07:46:45 PM
Designed Helical Peptides...bla bla bla...cleavage of membrane embedded proteins... eukaryotes...bla...bla...intramembrane proteolysis ...bla, bla, bla.
Hey, Mendel!
How's that GM corn coming along?
 
2007-05-15 07:49:42 PM
pathogenx

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Loosely translated means:

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I want what you are on!!!
 
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