Evolution of Red Giants

REFERENCE: Charpinet et al. “A compact system of small planets around a former red-giant star.” Nature (2011) 480, pgs 496 – 499.    

Red giants are low to intermediate mass stars late in their lifetimes that have swelled to massive sizes.  It has been predicted that the Sun will become a red giant is 7.5 billion years at which time its radius will become 200 times larger than it is now.  Typically, planets that are orbiting a star at a radius less than 1 astronomical unit (AU) will be engulfed by the swelling red giant.  However, some post red giant stars still have giant planets orbiting them at radii much closer than 1 AU.

                Recent work by Telting and colleagues suggests both how planets can survive immersion in the red giant envelope and influence the evolution of the star.  KIC 05807616 (also known as KPD 1943+4058) is a B subdwarf star, which is much hotter and brighter than a typical subdwarf star and represents a rarer way a red giant star can evolve.  This type of subdwarf evolves when a red giant loses its outer envelope prematurely.  Charpinet et al. show that KIC 05807616 has two planets, which they name KOI 55.01 and KOI 55.02, slightly smaller than Earth still orbiting it.

                They authors further offer a reasonable scenario as to how the current system came to be.  They feel that both bodies were originally large, gaseous planets that were swallowed by the red-giant envelope.  The immersion triggered the red giant’s outer shell premature loss and evolution into a B subdwarf, however this process stripped the planets of their gaseous layers and left only the inner cores, which the authors see orbiting the star today.

                An alternative scenario involving the merging of two white dwarfs that resulted in planet formation followed by a secondary planet is possible, but highly unlikely.

Ebolaviruses

REFERENCE: Dias et al. “A shared structural solution for neutralizing ebolaviruses.” (2011) Nature Structural and Molecular Biology 18(12) pgs 1424 – 1427.

                Five types of ebolaviruses have been identified: Sudan, Ebola, Reston, Bundibugyo, and Tai Forest.  The Sudan and Ebola forms cause the predominant amount of human deaths and recently a new variant of the Sudan virus has been found in the Gulu district of Uganda.  While many monoclonal antibodies exist, only a handful can neutralize Ebola virus and none can neutralize Sudan virus.  In a recent Nature Structural and Molecular Biology publication, Dias et al. discuss their development of a neutralizing antibody for Sudan virus and a subsequent crystal structure of it bound to the Gulu-Sudan variant protein GP_1,2.

                GP_1,2 (glycoprotein) is a viral trimeric receptor solely responsible for bringing ebolavirus into a host cell.  The protein is so named because the entire amino acid sequence is expressed then cleaved to create GP₁ and GP₂.  However, these two proteins remain attached to each other via a disulfide bond until the viral membrane fuses with the endosomal membrane.   

                The monoclonal antibody developed here, referred to as 16F6, recognized native Sudan virus GP_1,2 and their work indicated that binding of 16F6 alone was enough to block infection.  The epitope for the antibody was revealed by X-ray crystallography to be at the base of the trimer (Figure 11.1).  Further work showed that Sudan virus could still attach to host cells and be internalized, which left the authors to speculate that the antibody is either inhibiting another unidentified factor or it is blocking an additional necessary conformational change in GP_1,2 that leads to successful infection.  

                The final sentence of their paper summarizes a possible far-reaching conclusion from their work as “...for viruses in general, successful immunotherapy and vaccine design may depend on targeting antibodies that anchor glycoprotein subunits together and prevent the conformational changes required for fusion.”

How to: Autophosphorylation

REFERENCES:

Malecka & Peterson. “Face-to-Face, Pak-to-Pak.” (2011) Structure 19(12), pgs 1723 – 1724.

Wang et al. “Structural Insights into the Autoactivation Mechanism of p21-Activated Protein Kinase.” (2011) Structure 19(12), pgs 1752 – 1761. 

                Many kinases require the phosphorylation of a residue within their active site to help maintain a conformation that is compatible with substrate binding/kinase activity.  While some kinases are able to phosphorylate other kinases, many times it is the kinase itself which performs autophosphorylation.  However, it is an interesting question: if the kinase requires phosphorylation to function but it itself must provide the phosphorylation, how does that work?  It is nearly a “chicken or the egg” problem.

                In the issue of Structure published on December 6^th, two papers discuss the de novo phosphorylation of the Pak1 (p21-activated kinase 1) protein.  A commentary offered by Malecka and Peterson discuss the history of common mutations often used by bench scientists to achieve “kinase-dead” proteins that are useful for crystallization as well as an overview of other kinases whose crystal structures reveal dimeric structures where the active loop of one subunit is placed within the active site of the other subunit.  The authors discuss two ways in which kinases can transiently adopt active conformations within the dimer to achieve autophosphorylation in trans: symmetric and asymmetric.  Symmetric structures, such as those seen for the kinases Chk2 and Ire1, place each others activation loops in their active sites while asymmetric structures, such as DAPK3 and IGF1R, have only one subunit place its activation loop within the active site of the other subunit.  

                Pak1, as reported by Wang et al, adopts a symmetric trans-autophosphorylation structure.  Interestingly, the authors also report that the common lysine mutations made within the active site are not 100% kinase-dead so caution should be used when trusting them as such.