#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dominique Lessard and Dr. Dylan Verden of KIF1A.ORG summarize newly published KIF1A-related research and highlight progress in rare disease research and therapeutic development.
This week we have a very special edition of #ScienceSaturday that highlights a handful of recent advancements from KIF1A.ORG Research Network members and more!
KIF1A: An AI-written Poem
Last week we shared work from Arne Gennerich and Arne Sosa, where they used cutting edge techniques to investigate the structure of KIF1A. Similarly, Dr. Gennerich consulted the new and popular cutting edge AI service ChatGPT to create a poem about KIF1A. We think it created quite a beautiful ode to KIF1A!:
KIF1A, a molecule so fine,
With purpose to help cells combine.
It moves along, with grace and might,
Guiding packages, day and night.
Its journey starts, from neuron to nerve,
With precision, it always deserves.
It transports, with utmost care,
Important cargo, everywhere.
It never rests, nor takes a break,
In its mission, it always stays awake.
With power and speed, it travels on,
Making connections, until dawn.
KIF1A, a wonder of life,
A guardian of our nervous strife.
It helps us move, and think with ease,
A symbol of hope, in sickness and disease.
So here’s to KIF1A, a hero untold,
With a story, worth more than gold.
It’s a reminder, of the beauty inside,
A molecule, that we can’t hide.
Autoinhibited kinesin-1 adopts a hierarchical folding pattern
One of the most amazing things about the proteins in our body is all of the different shapes they form to do their jobs in the body. A long protein “string” will fold into in complex ways, much like a piece of paper being folded into origami, so that distant parts of the paper end up close to one another. Some sections of the protein may remain flat, while others are kinked like crease lines.
Many proteins can fold into multiple shapes. In the case of kinesins like KIF1A, the protein can fold into an active state to carry cargo, or into an inactive state. One important question for the switch between active/inactive is: Where are the “crease lines” in these proteins? In other words, which sections of the protein are important for making sure it can make the shapes it needs to? Historically, technical limitations oversimplify the complexity of these crease lines.
This is especially important because mutations can change the way these proteins fold, like unwanted creases in an origami diagram that mess up the intended shape. The better we understand the protein’s normal crease lines, the better we can anticipate, and develop treatments for, specific mutations.
Much like a piece of paper being folded into origami, KIF1A folds into complex shapes that are important for function.
This week we’re sharing a pre-print* that investigates where these crucial creases are in a KIF1A relative protein, kinesin-1. While KIF1A and kinesin-1 don’t have identical structure, the questions and methods in this paper could translate to KIF1A research (and good news, one of the authors on this paper, Dr. Kristen Verhey, is an engaged member of the KIF1A Research Network).
To ask these questions, the authors combined high resolution microscope images of kinesin-1 with a program called AlphaFold, which takes protein sequences and predicts what shape they will take on.
The authors then cut off sections of kinesin-1, or introduced mutations, and predicted the sequence again. This is like removing or adding creases and seeing how it changes the final shape. From this, they were able to find that kinesin requires multiple specific creases to stabilize its inactive shape. This could help researchers understand the consequences of mutations in these areas, or find compounds that specifically target these interactions!
*What’s a pre-print? Check out this #ScienceSaturday post to learn more
How Patients With Rare Diseases Are Accelerating Groundbreaking Research for Their Communities
Much of KIF1A.ORG’s work has been done with support from the Chan Zuckerberg Initiative’s Rare as One (RAO) Network, which has provided funds as well as access to a community of rare disease advocacy groups who share resources and best practices. This week as part of their #NoOrdinaryCampaign, the RAO Network released a short film that highlights our very own Luke Rosen and the TESS Foundation’s Kim Nye, and their journeys to find treatments for their rare disease communities.