ATP Synthase Shows Reason for ‘Slippage’

first_img(Visited 409 times, 1 visits today)FacebookTwitterPinterestSave分享0 The engine of life shows more engineering finesse with each new discovery.ATP synthase is surely one of the most amazing molecular machines we have reported on. Tiny but mighty, this rotary engine that runs on protons released from the food we eat is incredibly efficient, fast, and complicated. Being essential for all life, it challenges any kind of step-wise evolutionary origin. But for years, scientists wondered about a mismatch between its two halves.The motor consists of two parts, called F0 (which rotates powered by proton motive force), and F1 (where ATP is synthesized, yielding 3 ATP per revolution). The puzzling mismatch comes from the number of units in these two halves. Different species of ATP synthase have 8 to 17 “c subunits” in F0 (usually 10 to 12) that make up the carousel that rotates and turns the “gamma” central stalk, which acts like a camshaft connecting the two parts. The F1 part, though, has three pairs of two units. For every complete rotation of F0, with a corresponding rotation of the camshaft, three ATP are produced in F1. Why is there not a nice integer division between the two? How can 11 c subunits in F0 correspond to 3 ATP molecules in F1? Is there some slippage in the mechanism?ATP synthase is a rotary motor that generates 3 ATP per revolution.A new paper in Science Magazine sheds more light on this puzzle. In “Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F1-Fo coupling,” Murphy et al. address the issue: “An enduring question is how the stoichiometrically mismatched c ring in Fo (composed of 8 to 17 c subunits) and the three-fold symmetric F1 head are efficiently coupled.” The paper summary announces a reason for this mismatch that makes ATP synthase appear more and more like a “well-oiled machine”—They solved high-resolution cryo–electron microscopy structures of the ATP synthase complex, extracting 13 rotational substates. This collection of structures revealed that the rotation of the Fo ring and central stalk is coupled with partial rotations of the F1 head. This flexibility may enable the head to better couple continuous rotation with discrete ATP synthesis events.In other words, there is a slight rotation of the F1 head that not only synchronizes the two halves, but may actually contribute to the motor’s productivity. For those who like jargon,We find that the F1 head rotates together with the central stalk and c ring through approximately 30°, or one c subunit, at the beginning of each 120° step. Flexible coupling of the F1 head to the Fo motor is mediated primarily by a hinge at the interdomain link of the oligomycin sensitivity–conferring protein (OSCP) subunit that joins the F1 head to the peripheral stalk. The extended two-helix bundle of the central stalk γ subunit interacts with the catch-loop region of one β subunit of the F1 head. The resulting mechanism of flexible coupling is likely to be conserved [i.e., unevolved] in other F1-Fo ATP synthases. Our results provide much-needed context to a wealth of published data indicating that OSCP is a hub of metabolic control in the cell.This is an elegant design. It basically provides an interface between disparate parts, like a human-engineered”universal mount” with a flexible connector that can work with different models. The authors summarize this as follows:In ATP synthases, the F1 catalytic head can accompany the rotor through a rotation of ~30° at the beginning of each ~120° step. This movement allows flexible coupling of F1 and Fo. The interdomain hinge of OSCP facilitates flexible coupling and makes this subunit an apposite [def. “suitable; well-adapted; pertinent; relevant; apt”] point for the regulation of ATP synthesis.In addition, the authors found a metal ion (probably Zn+2) that may be involved in translating the proton flow into a torque. That’s another mysterious aspect of ATP synthase: how does a flow of protons actually turn the F0 motor? It’s been hard to tell, because that part of the engine is embedded in the membrane. They conclude, “A conserved [unevolved] metal ion in the proton access channel may synchronize c-ring protonation with rotation.” This hypothesis may require additional research. It might also be illuminating to investigate the diversity c subunits between species, to see whether there are reasons for 8, 10, 12, or 17 subunits depending on the environment, or whether they are due to neutral mutations which the conserved “flexible coupling” is designed to accommodate.Needless to say, the authors did not mention “evolution” in the paper.ATP synthase is a molecular machine you can use to “wow” your friends. “Did you know that you are running on rotary engines?” In simple terms, describe this waterwheel-like action that runs a mechanism that snaps ATP together, making 3 ATP per revolution. Tell them it is one of the most efficient engines ever discovered, but add that it is on the order of billionths of a meter in size. Tell them the protons come from the food you just ate, and that quadrillions of these little engines are spinning at over 6,000 RPM inside you right now. It might lead to some lively discussions about origins.last_img read more

Stay Humble. Stay Hungry.

first_imgStay HumbleIt doesn’t matter how well you are doing, or how much you are winning; you need to stay humble. Confidence is critical, but overconfidence is a killer.If you are number 1, know that there is someone, somewhere, who will somehow find a way to beat you. You may not know who they are, you may not believe it’s possible, and you may not see it coming. Right now, someone is gunning for you. They want your clients, and they want your spot.Stay humble. Know that you can see your blind spot, but your competitor just might. Believe that you still have work to do. Be pleased with your performance, without being completely satisfied.Stay HungrySuccess is funny. It can make you soft. You lose the tight belly that comes from being hungry. You can take your foot off the pedal and let up, coasting for a little while.If you are in first place, you have to challenge yourself to extend the lead, knowing that number 2 can very quickly become number 1. And number 1 can quickly fall a place or two.Stay hungry. Disrupt yourself before someone else does. Raise the bar, and stretch yourself. Set goals that are so high that you have to change what you are doing. Don’t allow yourself to believe your press clippings. The only press clippings that matter are the ones still to be printed.last_img read more

Suresh Kalmadi will not contest IOA election, hints at retirement

first_imgSuresh Kalmadi ‘s decision of not contesting elections comes exactly two years after the end of the 2010 Delhi Commonwealth Games which was hit by a series of corruption cases even before the start of the Games.Despite being arrested and spent some time in jail, Kalmadi had refused to step down from the post of president though he had written to the IOA acting chief V K Malhotra that he would not be involved in the day-to-to affairs for some time.This, however, did not stop the IOC from putting pressure on the IOA to remove Kalmadi and the world body, in a series of letters, said that it would send an election observer to monitor the polls as there was confusion on his status.Just a few days back, the IOC had asked the IOA to immediately suspend Kalmadi, along with his close aides in the CWG Organising Committee Lalit Bhanot and V K Verma till the disposal of the court cases against them. The world body had said that Kalmadi should also not be allowed to contest the IOA elections.With Kalmadi deciding not to seek re-nomination in the elections, the contest is likely to be between Indian Boxing Federation Chairman Abhay Chautala and incumbent IOA Secretary General Randhir Singh.Clean Sports India, a body fighting for corruption-free sports in the country, welcomed Kalmadi’s decision not to contest elections.”It is a welcome decision. We have been fighting for this. It is the beginning of a new era. The sports reforms can now be taken to its logical end,” B V P Rao, CSI convenor, said.He said former sportspersons should come into sports administration and start a new era.Kalmadi has been a Member of Parliament from 1982. He began his career with National Defence Academy and has been a flying instructor at Indian Air force team at NDA and has also participated in Indo-Pak war in 1965 and 1971 as an Air Force pilot.advertisementSuresh Kalmadi spent over a year in prison on corruption charges related to CWG scam.Kalmadi’s decision of not contesting elections comes exactly two years after the end of the 2010 Delhi Commonwealth Games which was hit by a series of corruption cases even before the start of the Games.Despite being arrested and spent some time in jail, Kalmadi had refused to step down from the post of president though he had written to the IOA acting chief V K Malhotra that he would not be involved in the day-to-to affairs for some time.This, however, did not stop the IOC from putting pressure on the IOA to remove Kalmadi and the world body, in a series of letters, said that it would send an election observer to monitor the polls as there was confusion on his status.Just a few days back, the IOC had asked the IOA to immediately suspend Kalmadi, along with his close aides in the CWG Organising Committee Lalit Bhanot and V K Verma till the disposal of the court cases against them. The world body had said that Kalmadi should also not be allowed to contest the IOA elections.With Kalmadi deciding not to seek re-nomination in the elections, the contest is likely to be between Indian Boxing Federation Chairman Abhay Chautala and incumbent IOA Secretary General Randhir Singh.Clean Sports India, a body fighting for corruption-free sports in the country, welcomed Kalmadi’s decision not to contest elections.”It is a welcome decision. We have been fighting for this. It is the beginning of a new era. The sports reforms can now be taken to its logical end,” B V P Rao, CSI convenor, said.He said former sportspersons should come into sports administration and start a new era.Kalmadi has been a Member of Parliament from 1982. He began his career with National Defence Academy and has been a flying instructor at Indian Air force team at NDA and has also participated in Indo-Pak war in 1965 and 1971 as an Air Force pilot.last_img read more

Vernon Philander Wins SA Cricketer of the Year

After a record-breaking season in which he captured 51 wickets in his first seven test matches, Vernon Philander was the big winner at the Cricket South Africa awards gala in Johannesburg on Wednesday evening.The Cape Cobras’ seamer lifted the prestigious South African Cricketer of the Year Award, and also received awards as Test Cricketer of the Year and the Fans’ Cricketer of the Year.Only Australia’s Charlie Turner reached 50 test wickets faster than Philander, but he played way back in 1888, in a time when scores were far lower and bowlers far more favored by pitches than they are today.Despite playing just those seven tests, he ranks seventh in International Cricket Council’s test bowling rankings. His test average is a miserly 14.15.ODI Player of the YearAB de Villiers was named ODI Player of the Year for the second time in succession after tallying 475 runs in eight games, including two centuries, at an astonishing average of 158.33 and a strike rate of 116.13.He also picked up an award decided upon by his peers when he was announced as the Players’ Player of the Year.Richard Levi won the CSA International T20 Cricketer of the Year and the KFC “So Good” awards, thanks to his stunning innings against New Zealand in Hamilton in February in which he struck a world-record equaling 117 not out. His runs came off only 51 balls, with a world record 13 sixes and five fours.Fast bowler Marchant de Lange, who captured 7 for 81 against Sri Lanka in Durban on his test debut, was named the Newcomer of the Year.Domestic awards winnersThe SuperSport Series Cricketer of the Year award went the way of Alviro Petersen, who played his way into the Proteas’ test line-up, while Faf du Plessis was named the Domestic Players’ Player of the Year.Matthew Maynard of the Titans was named Coach of the Year after leading the franchise to victory in the SuperSport Series and Twenty20 competitions.Earlier in the day, Shandre Fritz was named the Women’s Cricketer of the Year.Ewie Cronje, the father of the late Hansie Cronje, received a special lifetime achievement award for his years of service to Free State cricket. Under Cronje’s guidance, the province became a leading cricketing power in the country after having been mired in B-division cricket for decades.World rankingsA quick check on the health of South African cricket by looking at the latest ICC Player Rankings indicates that the country’s cricketers are doing very well.Among test batsmen, De Villiers ranks second, just ahead of Jacques Kallis, with Hashim Amla in ninth place.Dale Steyn enjoys a healthy lead among test bowlers, with Philander in seventh spot.Amla and De Villiers are ranked one and two among ODI batsmen, while Lonwabo Tsotsobe is in first place among ODI bowlers, with Morne Morkel in third position.Source: Southafrica.info read more

Dont learn classical music if you want a career Khan

first_imgSarod maestro Amjad Ali Khan has a word of caution for aspiring musicians, “Don’t learn classical music if you want a career.” “If you want to make a career then don’t learn classical music… Become an engineer, scientist or a bank manager.Classical music is a lifelong service, commitment and dedication to understand music,” Khan told PTI.The musician was here to perform at a charity concert held by Indian Cancer Society.Khan said only a few who can “entirely dedicate their lives to music and their masters” manage to find the light in the “dark tunnel that is music”. Also Read – Rian Johnson wants to move beyond ‘legacy characters’ with new ‘Star Wars’ trilogy”For music, you have to entirely dedicate yourself to the Gods and your teacher. Classical music is like entering a dark tunnel with this hope that some light will reach you someday.”A few of us find that light, while thousands of others are still stumbling around in the darkness,” Khan said.Pointing at the increasingly commercialised prospects of music, he said that people were learning music only “to make an album or to be on television”.”These days you see people who learn music to make an album, to appear on reality shows or to perform on stage. You don’t find many people who are learning music to actually understand music,” the Padma Vibhushan awardee said. Also Read – Making ‘Mission Mangal’ was a big risk: Akshay KumarWhile Khan disapproves of the commercialisation of music, he also feels that the “future of classical music is secure” in the hands of “talented” young aspiring musicians like his sons Amman and Ayaan and their contemporaries.”There are some very young talented musicians in this generation. Amaan, Ayaan and their contemporary musicians are very talented and they are quite established. So, I feel the future of classical music is secure,” he said.The Sarod player also noted that while legacy played its part in a musician’s life, it was largely his or her dedication and hard work that pays off.”It is not necessary that only a newcomer with a legacy can find his or her place in this field. Legacy helps, but not always.”I have taught Amaan and Ayaan classical music and Sarod, because music is my wealth, it is my property, bank balance, treasure and everything that I have. Now it’s up to their own hard work, commitment, dedication and discipline,” he said.last_img read more