Can I read Studying Protein Variation in Evolution, Disease, and Biology Through Deep Insertion, Deletion, and Missense Mutational Scanning on EtoBox?

Studying Protein Variation in Evolution, Disease, and Biology Through Deep Insertion, Deletion, and Missense Mutational Scanning by Christian B. Macdonald is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Studying Protein Variation in Evolution, Disease, and Biology Through Deep Insertion, Deletion, and Missense Mutational Scanning about?

Wolf-Hirschhorn syndrome, characterized by microcephaly, growth retardation, and epileptic seizures, indicating a fundamental function for LETM1 in humans. LETM1 contains a conserved Ca 2þ binding EF-hand motif (EF1). Deletion of EF1 abrogates LETM1 mediated mtCa 2þ flux, but the precise mechanism by which EF1 regulates exchanger function remains unknown. To begin understanding the role of EF1 in LETM1 function, we biophysical and structurally characterized isolated EF1. Our data show that EF1 exhibits augmented a-helical secondary structure, solvent exposed hydrophobicity and oligomerization in the presence of Ca 2þ due to a weak but specific, Ca 2þ -binding affinity. The low affinity is, in part, due to a terminal Asp within the binding loop, where mutation to Glu increases the affinity $4-fold. EF1 is structurally sensitive to pH changes within the physiological range for mitochondria, and remarkably, unfolds at high and low temperatures. Using solution NMR spectroscopy, we reveal that EF1 adopts an atypical EF-hand arrangement by pairing with an upstream loop-helix motif. Collectively, our data suggest that EF1 functions as a divergent multipartite environmental sensor within t

Who reads Studying Protein Variation in Evolution, Disease, and Biology Through Deep Insertion, Deletion, and Missense Mutational Scanning?

Author

Christian B. Macdonald

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)