Research Brief
Study Reveals Disease-Causing Protein's Structure
July 2, 2024
![Study Reveals Disease-Causing Protein's Structure](https://assets.montefioreeinstein.org/prod/styles/1440__fluid/s3/2024-08/hernando-sosa-study-reveals-disease-causing-proteins-structure.jpg.webp?VersionId=7fBABn6B2VKjmaJBQNeO84XvHY1f0HBE&itok=goSREA3l)
KIF1A-associated neurological disorders (KAND) are rare genetic conditions affecting some 580 families worldwide. These disorders are caused by mutations in the microtubule-associated motor protein KIF1A, which is essential for transporting cellular cargo along axons in neurons.
Hernando J. Sosa, Ph.D., Arne Gennerich, Ph.D., and their colleagues conducted cryo-electron microscopy studies to provide the first high-resolution structure of KIF1A bound to microtubules and to identify the structural defects of the KIF1A mutant P305L, a common and devastating mutation in children with KAND. Their findings revealed that structural changes in a part of the mutated P305L protein called the K-loop prevent the KIF1A mutant from binding properly to microtubules. Their structure-function studies showed that its K-loop critically determines KIF1A’s ability to move across long distances in axons. This research suggests that the K-loop could be a therapeutic target for restoring KIF1A function in individuals with KAND. The study published online on July 2 in Nature Communications.
Dr. Sosa and Dr. Gennerich are professors of biochemistry at Einstein.