Related Experiment Video

Updated: Aug 28, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the alpha beta spectrin

Patrick G Gallagher1, Zhushan Zhang, Jon S Morrow

  • 1Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA. patrick.gallagher@yale.edu

Laboratory Investigation; a Journal of Technical Methods and Pathology
|December 9, 2003
PubMed

Insights

This study identifies an alpha-spectrin mutation (Ile24Thr) causing severe hemolytic anemia in an infant. This genetic defect disrupts spectrin

Area of Science:

  • Hematology
  • Molecular Biology
  • Genetics

Background:

  • Neonatal hemolytic anemia and hyperbilirubinemia can present with complex erythrocyte abnormalities.
  • Elliptocytosis is a hereditary condition affecting red blood cell shape.
  • Spectrin is a critical protein in the erythrocyte cytoskeleton, maintaining cell integrity.

Observation:

  • An infant presented with severe neonatal hemolytic anemia and hyperbilirubinemia, progressing to ellipto-poikilocytic anemia.
  • The patient's father exhibited typical elliptocytosis.
  • Erythrocyte membrane analysis revealed structural and functional spectrin defects in both individuals.

Findings:

  • Genetic analysis identified a heterozygous alpha-spectrin mutation (Ile24Thr) in the spectrin self-association binding site in the proband and his father.
  • The proband also carried the alpha(LELY) low expression allele trans, modifying the clinical presentation.
  • Molecular modeling indicated that the Ile24Thr substitution disrupts essential hydrophobic interactions within the spectrin triple helix.

Implications:

  • This research highlights the crucial role of spectrin's alpha beta self-association site in maintaining erythrocyte stability.
  • The study underscores the impact of specific spectrin mutations on red blood cell structure and function, leading to hemolytic anemia.
  • Findings emphasize the importance of spectrin's evolutionary conserved residues for protein function and provide insights into hereditary elliptocytosis.

More Related Videos

Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System04:47

Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System

Published on: May 22, 2020

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions06:50

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

Published on: January 26, 2024

Related Concept Videos

Protein Folding01:49

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation which is critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.Protein Structure Is Critical to Its Biological FunctionProteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Mutations02:27

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously during DNA replication or be induced by environmental factors. Mutations can be characterized in several ways: by whether and how they alter the amino acid sequence of the protein, by the scale of the DNA affected, and by whether they affect somatic or germline cells.Consequences of Point Mutations at the Molecular LevelMutations that affect a single nucleotide are called point mutations. When point mutations...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...