Sea of Hypotheses

Hypothesis Testing: Putting Experiments where our mouths are

One Step Beyond: Making predictions

he whole point of our research, besides the generation of many-colored pictures, is to generate testable hypotheses about what the motor looks like as it does its work. So what we're really fishing for is a description of shapes of the motor--including which parts are touching at what times, and what the relative orientation of the parts is. The following links take you to some of the hypotheses our data (or wild imaginings!) have taken us to, and hopefully fill you in on just what we intend to do about it!

he CamShaft (amino acids 466-496) is a favorite resting spot of many of the original cold-sensitive mutants as well as a raft of suppressors. Clearly, the data is jumping up and down trying to tell us SOMEthing. Go to CamShaft=King to see what the cryptic message might be! Involvement of helix 466-496 in myosin conformational state.

he G680V mutation has been the subject of a lot of our biochemical and genetic analysis. As the first mutant to receive our full attention, it also represents a critical test of the validity of our approach. In order to justify this work, we must confront the question of whence cometh G680V suppressors and are they just a bunch of 'noise' or is there a molecular message inscribed in their identities and locations? Effects of G680V and its suppressors on opening of 'back door' (= Pi release)

ur 'big picture' goal is to sketch out the conformations the motor adopts as it goes through its cycle. We have now amassed enough suppressor data that we're starting to be able to perceive mutant 'families'--groups that behave similarly (from a genetic standpoint). To see how and why we think this is shining light on dark parts of the motor's cycle, check out It's a Family Affair. Identifying conformational states using suppressor 'families'.

ne of the more intriguing suppressors we have come across is E150K. This mighty suppressor is capable of restoring life to the N483S, Y494K, W501L and G691C mutations! Yet it lives on the surface of myosin out of the immediate neighborhood of the hapless mutations it revives. Wherein is the secret of E150K's marvelous powers?

erhaps the deepest, darkest mystery of myosin is its interactions with actin. While absolutely critical to the motor function of myosin (since actin is the object gripped and moved by the motor) our access to information about these states is fleeting and of low resolution. Of course, genetic information can shine a bright light down these dark tunnels; go to the Quivering Chin to see what's up (or down, as the case may be...). Unanticipated conformational re-arrangement of lower jaw (= lower 50K domain)

he Holy Grail of this whole enterprise is to sketch out conformations of the motor that we have yet to observe through other methods. This is an ambitious goal, but I think we're starting to achieve some success here. A recent rash of suppressor sightings is focusing our attention at one position of the CamShaft. To see a place where the Whale Turns, check out Tossin' and Turnin' Analysis of M486 and the bending of the CamShaft observed in the ADP.vanadate structure vs. other structures.

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2 Wrong
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Fixing mutants
the hard way


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Bruce Patterson