Related Experiment Video
Updated: Jul 17, 2026
10:40
Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
Evolutionarily conserved structural and functional roles of the FYVE domain
Akira Hayakawa1, Susan Hayes, Deborah Leonard
1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Biochemical Society Symposium
|January 20, 2007
Summary
The FYVE domain binds phosphoinositide PtdIns3P, crucial for early endocytosis. Its variable cell interactions, influenced by oligomerization and membrane binding, regulate protein function.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The FYVE domain is an 80-amino acid motif that specifically binds phosphoinositide PtdIns3P.
- FYVE domains are present in 38 human proteins, fewer in C. elegans and D. melanogaster, with eight conserved across species.
- Some proteins have lost FYVE domains during evolution, suggesting functional adaptation.
Purpose of the Study:
- To investigate the evolutionary conservation and functional significance of FYVE domains.
- To explore the mechanisms underlying the variable interactions of FYVE domain-containing proteins with endosomes.
- To understand how FYVE domain properties regulate protein function in early endocytosis.
Main Methods:
- Comparative genomics to assess FYVE domain conservation across species.
- RNA interference (RNAi) screen in C. elegans to identify functional roles (e.g., WDFY2 in endocytosis).
- Biochemical and biophysical analyses to characterize FYVE domain interactions with PtdIns3P and cell membranes.
Main Results:
- Eight FYVE domains are conserved across humans, C. elegans, and D. melanogaster, including uncharacterized proteins like WDFY2 involved in early endocytosis.
- Evolutionary loss of FYVE domains in some proteins (e.g., Rabatin-5 homologue) suggests adaptation of PtdIns3P and Rab GTPase signaling pathways.
- In vitro PtdIns3P binding does not always correlate with in vivo endosome interaction due to variations in oligomerization, membrane insertion, and electrostatic interactions.
Conclusions:
- FYVE domain-containing proteins play conserved roles in endocytosis, with evolutionary pressures shaping their domain composition.
- The variable ability of FYVE domains to interact with endosomes is determined by specific residues influencing oligomerization, membrane insertion, and electrostatic interactions.
- These distinct biophysical properties fine-tune the localization and duration of FYVE protein interactions with early endosomes, thereby modulating their biological functions.
Related Concept Videos
01:49Conserved 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...
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...
01:49Conserved 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...
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...
01:56Structural Protein Function
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
01:56Structural Protein Function
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
02:26Conservation of Protein Domains
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...