Here we present the first full anatomical description of the 3.67 million-year-old Australopithecus skull StW 573 that was recovered with its skeleton from the Sterkfontein Member 2 breccia in the ...Silberberg Grotto. Analysis demonstrates that it is most similar in multiple key morphological characters to a group of fossils from Sterkfontein Member 4 and Makapansgat that are here distinguished taxonomically as Australopithecus prometheus. This taxon contrasts with another group of fossils from those sites assigned to Australopithecus africanus. The anatomical reasons for why these groupings should not be lumped together (as is frequently done for the South African fossils) are discussed in detail. In support of this taxonomy, we also present for the first time a newly reconstructed palate of A. africanus (StW 576 from Sterkfontein Member 4), which has a uniquely complete permanent dentition. The StW 573 skull also has certain similarities with other earlier Australopithecus fossils in East Africa, assigned to Australopithecus afarensis and Australopithecus anamensis, which are discussed. One of its most interesting features is a pattern of very heavy anterior dental wear unlike that found in A. africanus but resembling that found in A. anamensis at 4.17 Ma. Because the StW 573 skull is associated with a near-complete skeleton that is also described for the first time in this special issue, we are now able to use this individual to improve our understanding of more fragmentary finds in the South African fossil record of Australopithecus.
The kinetics of conformational changes of P-type ATPases necessary for the occlusion or deocclusion of transported ions are known to be sensitive to the composition of the surrounding membrane, e.g., ...phospholipid content, mole percentage of cholesterol, and the presence of lipid-bound anions. Research has shown that many membrane components modify the dipole potential of the lipid head-group region. Based on the observation that occlusion/deocclusion reactions of ion pumps perturb the membrane surrounding the protein, a mechanism is suggested whereby dipole potential modifiers induce preferential stabilization or destabilization of occluded or nonoccluded states of the protein, leading to changes in the forward and backward rate constants for the transition. The mechanism relies on the assumption that conformational changes of the protein are associated with changes in its hydrophobic thickness that requires a change in local lipid packing density to allow hydrophobic matching with the membrane. The changes in lipid packing density cause changes in local lipid dipole potential that are responsible for the dependence of conformational kinetics on dipole potential modifiers. The proposed mechanism has the potential to explain effects of lipid composition on the kinetics of any membrane protein undergoing significant changes in its membrane cross-sectional area during its activity.
Peptide ligation chemistry has revolutionized protein science by providing access to homogeneously modified peptides and proteins. However, lipidated polypeptides and integral membrane proteinsan ...important class of biomoleculesremain enormously challenging to access synthetically owing to poor aqueous solubility of one or more of the fragments under typical ligation conditions. Herein we describe the advent of a reductive diselenide-selenoester ligation (rDSL) method that enables efficient ligation of peptide fragments down to low nanomolar concentrations, without resorting to solubility tags or hybridizing templates. The power of rDSL is highlighted in the efficient synthesis of the FDA-approved therapeutic lipopeptide tesamorelin and palmitylated variants of the transmembrane lipoprotein phospholemman (FXYD1). Lipidation of FXYD1 was shown to critically modulate inhibitory activity against the Na+/K+ pump.
Lipid-protein interactions are normally classified as either specific or general. Specific interactions refer to lipid binding to specific binding sites within a membrane protein, thereby modulating ...the protein’s thermal stability or kinetics. General interactions refer to indirect effects whereby lipids affect membrane proteins by modulating the membrane’s physical properties, e.g., its fluidity, thickness, or dipole potential. It is not widely recognized that there is a third distinct type of lipid-protein interaction. Intrinsically disordered N- or C-termini of membrane proteins can interact directly but nonspecifically with the surrounding membrane. Many peripheral membrane proteins are held to the cytoplasmic surface of the plasma membrane via a cooperative combination of two forces: hydrophobic anchoring and electrostatic attraction. An acyl chain, e.g., myristoyl, added post-translationally to one of the protein’s termini inserts itself into the lipid matrix and helps hold peripheral membrane proteins onto the membrane. Electrostatic attraction occurs between positively charged basic amino acid residues (lysine and arginine) on one of the protein’s terminal tails and negatively charged phospholipid head groups, such as phosphatidylserine. Phosphorylation of either serine or tyrosine residues on the terminal tails via regulatory protein kinases allows for an electrostatic switch mechanism to control trafficking of the protein. Kinase action reduces the positive charge on the protein’s tail, weakening the electrostatic attraction and releasing the protein from the membrane. A similar mechanism regulates many integral membrane proteins, but here only electrostatic interactions are involved, and the electrostatic switch modulates protein activity by altering the stabilities of different protein conformational states.
This article of the continuing “
Biophysical Reviews
Meet the Editors Series” introduces Ronald Clarke, biophysical chemist, member of the
Biophysical Reviews
editorial board and current ...Secretary-General of the International Union of Pure and Applied Biophysics (IUPAB).
Sterkfontein is the most prolific single source of
Australopithecus
fossils, the vast majority of which were recovered from Member 4, a cave breccia now exposed by erosion and weathering at the ...landscape surface. A few other
Australopithecus
fossils, including the StW 573 skeleton, come from subterranean deposits T. C. Partridge
et al.
,
Science
300, 607–612 (2003); R. J. Clarke, K. Kuman,
J. Hum. Evol.
134, 102634 (2019). Here, we report a cosmogenic nuclide isochron burial date of 3.41 ± 0.11 million years (My) within the lower middle part of Member 4, and simple burial dates of 3.49 ± 0.19 My in the upper middle part of Member 4 and 3.61 ± 0.09 My in Jacovec Cavern. Together with a previously published isochron burial date of 3.67 ± 0.16 My for StW 573 D. E. Granger
et al.
,
Nature
522, 85–88 (2015), these results place nearly the entire
Australopithecus
assemblage at Sterkfontein in the mid-Pliocene, contemporaneous with
Australopithecus afarensis
in East Africa. Our ages for the fossil-bearing breccia in Member 4 are considerably older than the previous ages of ca. 2.1 to 2.6 My interpreted from flowstones associated with the same deposit. We show that these previously dated flowstones are stratigraphically intrusive within Member 4 and that they therefore underestimate the true age of the fossils.
The cave infills at Sterkfontein contain one of the richest assemblages of Australopithecus fossils in the world, including the nearly complete skeleton StW 573 ('Little Foot') in its lower section, ...as well as early stone tools in higher sections. However, the chronology of the site remains controversial owing to the complex history of cave infilling. Much of the existing chronology based on uranium-lead dating and palaeomagnetic stratigraphy has recently been called into question by the recognition that dated flowstones fill cavities formed within previously cemented breccias and therefore do not form a stratigraphic sequence. Earlier dating with cosmogenic nuclides suffered a high degree of uncertainty and has been questioned on grounds of sediment reworking. Here we use isochron burial dating with cosmogenic aluminium-26 and beryllium-10 to show that the breccia containing StW 573 did not undergo significant reworking, and that it was deposited 3.67 ± 0.16 million years ago, far earlier than the 2.2 million year flowstones found within it. The skeleton is thus coeval with early Australopithecus afarensis in eastern Africa. We also date the earliest stone tools at Sterkfontein to 2.18 ± 0.21 million years ago, placing them in the Oldowan at a time similar to that found elsewhere in South Africa at Swartkans and Wonderwerk.
PDF
