Faculty of 1000

Post-publication peer review

Waltzing Mathilda

Posted by rpg on 17 March, 2010

You turn me right round

As an undergraduate, I remember being fascinated by the family of rotary motors that is the proton-translocating ATPase. This is the protein complex, resembling something from the imagination of E. E. ‘Doc’ Smith rather than anything merely biological, that either pumps protons from one side of a membrane to another, or uses a proton gradient to drive its rotation and make ATP. One of the less obvious difficulties with this amazing piece of machinery is that because the thing rotates, you need something to counteract the torque generated. So the ATPase has a additional stator component, the peripheral stalk, that links the nucleotide-binding domain to the membrane-embedded domain, which stops the entire thing waltzing away.

Interestingly, despite its essential role, the peripheral stalk is the least conserved element of the structure, varying in composition and number of subunits across the family. Daniela Stock’s lab at the Victor Chang in Sydney has recently published the structure of the peripheral stalk of the Thermus thermophilus H+-ATPase/synthase, in the process discovering a new protein structural motif—a right-handed hetereodimeric coiled-coil.

peripheral stalk

And that’s fascinating because the central stalk contains a left-handed coiled-coil, and it’s tempting to speculate that the opposite coiling of the two stalks is important, either in stabilizing the whirligig and/or for proton pumping. Read all about it (free link):

This paper reports, for the first time, a crystal structure of the bacterial A/V-ATP synthase peripheral stalk complex, which shows the N-terminal domains of the two peripheral-stalk-forming subunits E and G to be folded in a heterodimeric right-handed coiled coil, a protein fold not seen before.

Stephan Wilkens

Some shall pass

Peroxisomes can import fully-folded, native proteins across their lipid bilayer. How they achieve this wasn’t known—hypotheses included the transient formation of pores or a process similar to endocytosis (compare with the nucleus, for example, which transports macromolecules in and out via stable pores existing within the double membrane). It turns out that the membrane-associated receptor Pex5p, which recognizes the peroxisome signal motif Ser-Lys-Leu at the C-terminus of potential cargo, forms a highly dynamic, ion-conducting channel in conjunction with its docking partner Pex14p and cargo. These transient pores can be opened to a diameter of about 9 nm, allowing quite large protein complexes to pass. (Meinecke et al., Nat Cell Biol)

Who are you?

Whole genome sequencing is getting a fair bit of press recently. The ‘$1000 genome’ is still a way off; but a case can be made that even the current cost (~$50,000 and dropping) compares favourably with current diagnostic procedures for genetically heterogenous conditions. A paper in NEJM shows the feasibility of using whole genome sequencing to identify clinically relevant variants in the case of a rare, inherited disease, and provide diagnostic information to inform the care of patients:

the patient described is a compound heterozygote for two different missense mutations, which are easily missed in standard sequencing-based strategies for mutation identification.

(Free F1000 evaluation)

And finally, don’t forget to check out the Faculty Faves at The Scientist homepage. These are selected from the previous day’s most interesting papers at F1000, and available for free.

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