Wednesday, 22 March 2023

Yet more evidence of technology all the way down.

A Biochemical Icon of Intelligent Design, ATP Synthase Does More than Spin

The biochemical icon of rotary machines, ATP synthase, remains in the news with new discoveries. Now that cryo-electron microscopy is widely used, biophysicists are looking at the function of individual subunits of the engine and figuring out what they do. The fact that molecular machines exhibit more functional elegance the closer one looks indicates that intelligent design is the best explanation.

Automatic Brake

Animals and plants both contain these vital rotary engines that supply their energy needs in ATP. In animals, they are found in mitochondria. In plants and other photosynthetic organisms, they are found in chloroplasts. Photosynthesis, being dependent on light, has a problem: when it’s dark, their rotary engines might start running in reverse, risking “a wasteful ATP hydrolysis reaction.”

Working with the green alga Chlamydomonas reinhardtii (pictured above) as a “model organism,” a team of eight Japanese scientists took a closer look at the γ subunit in chloroplast ATP synthase (this is the “camshaft” part of the engine that drives the synthesis of ATP in the F1 domain). They found that two specific domains in the γ subunit act as an automatic brake in the dark. They wrote in PNAS in January,

Among the FoF1-ATP synthase complexes of all organisms, chloroplast FoF1 (CFoCF1) is a unique enzyme with a redox regulation mechanism; however, the underlying mechanism of redox regulation of the adenosine triphosphate (ATP) synthesis reaction in CFoCF1 has not been fully elucidated. By taking advantage of the powerful genetics of Chlamydomonas reinhardtii as a model organism for photosynthesis, we conducted a comprehensive biochemical analysis of the CFoCF1 molecule. Here we identify structural determinants for the kinetics of the intracellular redox response and demonstrate that the redox regulation of ATP synthesis is accomplished by the cooperative interaction of two γ subunit domains of CFoCF1 that are unique to photosynthetic organisms.

Figure 6 in the article (reproduced by Phys.org) shows how the two domains act like a

stopper:

The tight conformation weakens the interaction between the redox loop and the β-hairpin. Consequently, the β-hairpin remains stuck in the cavity between the α and β subunit, like a stopper, and inhibits the rotation of the central stalk (γεc-ring). In a reduced form, the redox loop recovers flexibility to interact with the β-hairpin. The redox loop interacts to pull out the β-hairpin from the cavity and thus accelerates the central stalk, like a cooperative regulator.

Watching the Snap

Another Japanese team, this one from the University of Tokyo, looked closer at the “catalytic dwell” in the F1 domain of the ATP synthase engine where ADP is converted to ATP with the addition of a phosphate. The F1 domain has 3 pairs of α, β subunits arranged like petals of a flower, each pair in a different phase of activity: insertion of ingredients, catalysis, and ejection of ATP. The γ subunit, like a camshaft, activates each α, β pair in turn as it rotates a full 360°. Dividing by three, each α, β pair feels the force of the camshaft during the catalysis stage (ADP + P yielding ATP) within 120° at each full turn of the crankshaft. At the other times, the pair is either receiving the ingredients or ejecting the finished ATP. When running in reverse, the F1 motor becomes an ATP cleaver, hydrolyzing ATP to yield ADP and P, ejecting protons in the process. In hydrolysis, then, ATP becomes the fuel to make the motor run in reverse.

During normal operation, the motor catalyzes ATP. Biophysicists have long suspected that the camshaft (the γ subunit) exerts pressure on the incoming ADP and P to snap them together. If 0° represents the moment ATP is catalyzed, previous studies have found a short pause stage at 80° and a longer dwell at the subsequent 40° of rotation, representing the “chemomechanical coupling scheme,” as their Paper calls it.

In the reverse reaction, though, the angle for cleavage of ATP was unclarified. The team made a hybrid ATP synthase that ran extremely slowly so that they could observe “the world’s

smallest rotary biological molecule motor” running in reverse. Their hybrid allowed them to measure the angle at which ATP cleavage occurs.

As a result, the new hybrid F1 showed two pausing angles that are separated by 200°. They are attributable to two slowed reaction steps in the mutated β, thus providing the direct evidence that ATP cleavage occurs at 200° rather than 80° subsequent to ATP binding at 0°. This scenario resolves the long-standing unclarified issue in the chemomechanical coupling scheme and gives insights into the mechanism of driving unidirectional rotation.

See the “Graphical Abstract” in the paper that illustrates this “extremely long dwell” they measured. The finding reveals that in both directions, ATP synthase is finely tuned for its work. The reverse direction (hydrolysis) is not just like a motor leaking fuel. Its parts act with precision to cleave ATP in a specific way.

Insights into a Related Rotary Motor

There’s a cousin to ATP synthase. It’s a proton pump called V-ATPase (vacuolar-type adenosine triphosphatase), and its catalytic parts are labeled V1Vo instead of F1Fo. Like its counterpart, V-ATPase runs with a rotary action but spends ATP to pump protons into organelles. Its job is to acidify vacuoles and other organelles or intracellular compartments that need a lower pH to work. The Vo part pumps the protons (H+ ions) into the vacuole, increasing its acidity. A little thought shows that such a motor could be dangerous. Would you want an acid-generating motor running loose?

Scientists from a Toronto hospital, publishing in PNAS, were curious to figure out how these acid pumps get built without causing harm to the cell. The Vo complex is assembled in the endoplasmic reticulum (ER) and then transported to the Golgi apparatus to be combined with V1. What quality control mechanism keeps the domains inactivated until they are fully assembled and ready for action?

Using cryo-electron microscopy, the team imaged three proteins (Vma12p, Vma22p, and Vma21p) that must work together to achieve the quality control for safely handling the acid pumps during assembly. “The resulting structures,” they found, “show how a sequence of coordinated interactions and conformational changes ensures that only properly assembled Vo leaves the ER and proton pumping into the neutral ER is avoided.” Spilling acid into the ER could be bad! “Unsurprisingly,” they remark, “owing to their importance for Vo assembly, mutations in the human homologues of Vma12p, Vma22p, and Vma21p have been linked to disease.” So how do these three essential proteins perform quality control? Do you really want to know?

The structures described above suggest the sequence of events that occur during Vo assembly in the ER membrane and subsequent binding of V1 in the Golgi…. The c ring assembles around Voa1p, with binding of subunit d to the c8c′c″Voa1p ring masking the ER-retrieval motif of Voa1p. The Vo∆aef:Vma12-22p structure indicates that the Vma12-22p complex binds this fully assembled ring prior to interaction with subunits a, e, and f (Fig. 4A). Vma12-22p helps recruit and secure the interaction of subunit a with the c ring through interaction of Vma12p with subunits a and d….

Their Final Sentence

OK, OK. Suffice it to say that a complicated set of interactions takes place to ensure V-ATPase assembly is safe! Biochemists may wish to labor through the details. Fortunately, the authors provided diagrams and animations to illustrate the dynamics of all these working parts. Note their final sentence: “Importantly, the structures illustrate how Vma21p and Vma12-22p play central roles in both V-ATPase assembly and quality control.”

Quality control: it’s an engineering concept that permeates all three of these studies. Without quality control, these nanoscopic rotary engines, on which all life depends, would never last — indeed, would never emerge in the first place. Quality control belongs in the working vocabulary of intelligent design and engineering. It is not found in Darwin’s dictionary.

Junk DNA trope continues to be exposed as Junk science?

More Jobs for “Junk” DNA (Cont.)

Paul Nelson

If “junk” DNA goes toxic, does that suggest it had an original normal function? See the conclusion of this new paper, “Native functions of short tandem repeats”

Historically, repetitive elements within human genomes have been viewed as mostly unregulated ‘junk DNA’ that is not under selective evolutionary pressure. As such expansions of these repetitive elements are unfortunate accidents which become apparent and important only when they elicit highly penetrant and syndromic human diseases. Consistent with this line of reasoning, the field of REDs [Repetitive Element Diseases] has largely focused on emergent toxic mechanisms as drivers of disease only in the setting of large STR [Short Tandem Repeats] expansions rather than considering their pathology as alterations in the native functions played by these repeats in their normal genomic contexts. Here, we propose re-framing the discussion around repetitive elements in general — and STRs in particular — within human genomes. For each STR, we suggest first considering whether the STRs associated with a human disease have any native functions at their ‘normal’ size. If a native function exists, then expansion of these STRs can be viewed primarily as an aberrancy of that native function with coincident predictable impacts on gene expression dysregulation above certain repeat lengths. This reframing aligns with the approach typically taken in studying gain-of-function and loss-of-function mutations in disease associated single amino acid mutations and better ties the native functions of STRs to their pathology. It also suggests that shared regulatory rules will likely apply across REDs.

The article by Shannon E. Wright and Peter K. Todd is open access at eLife. Of course, lots of so-called “junk” has turned out to be functional. For another recent example, see Here

The real ocean master?

When man leapt to the moon.

The central nervous system of the warmachine?

The boogaloo begins?

Indoctrination makes science boring?

Gilson: How a Teacher Wrecked Biology for Me, and How I Got Past It

Evolution news

On a new episode of ID the Future, Tom Gilson, a writer and editor for The Stream, shares his experiences in high school biology. Important mysteries (i.e., major problems) with evolutionary theory were hurried past and papered over, yet his biology teacher could take an entire class period to tell Charles Darwin’s life story, and then repeat the same class, virtually verbatim, five more times that same semester. Hear how the class put Tom Gilson off of biology, but how he now finds the subject fascinating, thanks to the work of intelligent design researchers and the larger community of life scientists. Download the podcast or listen to it Here.

Gilson’s commentary is taken from, and builds on, a recent essay of his, available at Evolution News.

Operating in the shadows.

ID is perfectly natural?

Let’s Help Harvard Understand Intelligent Design

Jonathan McLatchie

Last week, my wife and I spent an afternoon at the Harvard Museum of Natural History, in Cambridge, MA, near where we live. We both were generally impressed by the exhibitions, particularly the dinosaur section, and would recommend the museum to anyone visiting Boston. I was, however, quite disappointed to see this notice at the entrance to the display on evolution:

It was disappointing to see the inaccurate representation of intelligent design (ID), along with the poor scientific epistemology.

A “Super-Natural Explanation”?

First, proponents of ID have long stressed that ID, in its purest sense, does not necessarily postulate a supernatural cause but is consistent with a natural or supernatural intelligence. Furthermore, I would contend that the natural / supernatural distinction is problematic. What precisely is meant when a phenomenon is described as supernatural, and by what set of criteria is it distinguished from the natural? Often, the word “supernatural” is used to describe the capacity to perform miracles, defined as violations of natural law. I would, however, offer a more nuanced definition of a miracle, which is that a miracle describes an interruption in the way nature normally behaves when left to itself. A miracle does not violate natural law, because natural law only describes what happens when nature is left to itself – not what happens when there is an intervention by an external agent. I am not by any means the first to define a miracle in these terms. Indeed, the atheist philosopher John Mackie in his classic book, The Miracle of Theism, defines a miracle along similar lines.1 As agents ourselves, we have the capability of interrupting the normal course of nature, determined by natural law. When I consciously choose to catch a ball with my hands, I am interrupting the trajectory it would have otherwise taken if left to itself. Agency itself is not governed by natural law, nor can it be reduced to material constituents. Human free will — my belief in which I take to be strongly justified by direct acquaintance — is, in my view, utterly incompatible with a materialistic reductionist perspective on the mind. Since, in my judgment, the strong burden of proof required to demonstrate that the strong appearance of free agency is merely illusory has not been met, this provides a strong prima facie justification for believing the mind to not be reducible to material components. Few would want to use the term “supernatural” to describe the human mind. A more helpful distinction, then, is between material and non-material causes. But non-material causes — assuming my judgment about the non-reducibility of agency to be correct — are already demonstrably a part of the natural world, since all of us have minds. Thus, the fact that ID postulates a non-material entity cannot be used to exclude ID from the natural sciences. Moreover, if our epistemology arbitrarily excludes one possible answer to an inquiry a priori, there is a real danger of being led to an incorrect conclusion about the natural world.

“Observation”

Second, the invocation of an unobservable entity should not be a demarcating factor that renders ID unscientific, for that would exclude other scientific disciplines, such as particle and nuclear physics, as well. Unobservable entities can often be detected by their effects, even without direct observation. For example, black holes are not directly observable since they do not emit electromagnetic radiation that can be detected with telescopes. Their existence and presence, however, is inferred by the effects that they exert on nearby matter, since gas flowing around a black hole increases in temperature and emits radiation that can be detected (their gravitational effects on surrounding objects, such as nearby stars, and the bending of light passing by a black hole, can also reveal the presence of a black hole).

“Testing”

Third, ID is testable in the same way that other hypotheses purporting to explain events in the distant past (including evolution by natural selection) are tested — by the historical abductive method of inference to the best explanation.2 Given that functionally specific information content is, in every other realm of experience, habitually associated with conscious activity and no other category of explanation has been demonstrated to be causally sufficient to account for its origin, ID is the most causally adequate explanation of the relevant data.

“Predictions”

Fourth, a scientific theory can be well justified even if it does not make strong predictions; it just needs to render the evidence significantly more probable than it would have otherwise been. For example, the hypothesis that you were in the vicinity of a nuclear plant does not strongly predict that you will have radioactive poisoning (few such workers suffer this). But if you did have radioactive poisoning, it would be significant evidence that you were in the vicinity of a nuclear plant since that data is more expected (or, less surprising) given the truth of the hypothesis than given its falsehood. Thus, even if ID only weakly predicts the observed data, it can still be strongly justified if the data is extremely unlikely if ID is false. ID, I would argue, also has a reasonably high intrinsic plausibility (what probability theorists call prior probability) given the independent evidence of there being a mind behind the universe who has an interest in creating complex life (that is, the evidence of cosmic fine tuning3 and prior environmental fitness4). It shouldn’t be too surprising, then, if the data also indicate that life was purposely brought about.

An “Inherent Conflict”?

Fifth, ID is not postulated because there is a perceived incompatibility between evolution and religion, but rather because we understand it to be the best interpretation of the scientific evidence. That being said, the “many scientists and religious leaders” who “do not perceive an inherent conflict between religion and the scientific theory of evolution” are correct that God and naturalistic evolution are logically compatible. However, naturalistic evolution, if true, would constitute significant evidence against theism and by extension religion. Why? First, if the conclusion that teleology best explains biological phenomena is evidence for theism, it necessarily follows that the falsehood of this conclusion would be evidence against theism. Second, atheism, and in particular naturalism (which, I would contend, is the most consistent version of atheism), strongly predicts that there be a naturalistic evolutionary account of life’s origins and development on earth. However, this is significantly less well predicted by theism. Therefore, though not by itself sufficient grounds on which to reject theism, unguided evolution — being more surprising given theism than given atheism — would, if true, constitute significant evidence against theism.It is unfortunate that the administrators of the Harvard Museum of Natural History seem to have failed to do their due diligence to understand the claims of ID, and how its advocates propose to test it, before dismissing it as being outside of the scope of science.

On the roots of the interslavic conflict?

The new Roman empire.

meditations of aservantofJEHOVAH

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