Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.

Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

Conservation of Protein Domains Over Different Proteins

Conservation 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...

The Proteasome Structure

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

CTCF directly binds G-quadruplex structures to regulate genome topology and gene expression.

Proceedings of the National Academy of Sciences of the United States of America·2026

Same author

Per-ARNT-Sim (PAS) Domains in Basic Helix-Loop-Helix (bHLH)-PAS Transcription Factors and Coactivators: Structures and Mechanisms.

Journal of molecular biology·2023

Same author

Histone acetylation and deacetylation - Mechanistic insights from structural biology.

Gene·2023

Same author

Prostaglandins as Candidate Ligands for a Per-ARNT-Sim (PAS) Domain of Steroid Receptor Coactivator 1 (SRC1).

bioRxiv : the preprint server for biology·2023

Same author

Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex.

Nature communications·2023

Same author

A Novel Mechanism of Coactivator Recruitment by the Nurr1 Nuclear Receptor.

Journal of molecular biology·2022

Search research articles

Related Experiment Video

Updated: Jul 12, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Structural basis for ubiquitin recognition by SH3 domains.

Yuan He¹, Linda Hicke, Ishwar Radhakrishnan

¹Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.

Journal of Molecular Biology

|September 4, 2007

Summary

The study reveals how the Sla1 SH3 domain binds ubiquitin, a key signaling molecule. This interaction, crucial for endocytosis, involves a unique binding surface and a critical phenylalanine residue.

More Related Videos

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Related Experiment Videos

Last Updated: Jul 12, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Area of Science:

Molecular Biology
Structural Biology
Cell Biology

Background:

SH3 domains are common protein-protein interaction modules in signaling and adaptor proteins.
SH3 domains of endocytic proteins can bind ubiquitin, a signal for cellular processes like endosomal sorting and protein degradation.

Purpose of the Study:

To determine the solution NMR structure of ubiquitin in complex with the SH3 domain of the yeast endocytic protein Sla1.
To elucidate the molecular basis of the SH3-ubiquitin interaction and its implications for protein function.

Main Methods:

Solution Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the structure of the complex.
Structural analysis focused on identifying the ubiquitin binding surface of the Sla1 SH3 domain.

Main Results:

The Sla1 SH3 domain binds ubiquitin via a surface that overlaps with its canonical proline-rich ligand binding site.
The interaction engages the Ile44 hydrophobic patch of ubiquitin, a common feature of ubiquitin-binding motifs.
A phenylalanine residue within the SH3 domain is identified as a key determinant for ubiquitin binding specificity.

Conclusions:

The determined structure provides insight into how SH3 domains can adopt non-canonical functions, such as ubiquitin binding.
This finding expands our understanding of ubiquitin signaling pathways and the versatility of SH3 domains in cellular processes.