Related Experiment Video

Updated: Feb 12, 2026

Whole-cell Patch-clamp Recordings for Electrophysiological Determination of Ion Selectivity in Channelrhodopsins
08:39

Whole-cell Patch-clamp Recordings for Electrophysiological Determination of Ion Selectivity in Channelrhodopsins

Published on: May 22, 2017

18.1K

Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors

Ken-Ichi Miyazono1, Saho Moriwaki1, Tomoko Ito1

  • 1Laboratory of Basic Science on Healthy Longevity, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

Science Signaling
|March 29, 2018
PubMed

Insights

Transforming growth factor-β (TGF-β) signaling relies on SMAD proteins binding cofactors. Crystal structures reveal how SMAD2 and SMAD3 proteins use specific surface patches to select cofactors, controlling gene expression and TGF-β pathway output.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Structural Biology

Background:

  • Transforming growth factor-β (TGF-β) signaling regulates critical cellular functions like proliferation and immune responses.
  • Dysregulation of TGF-β signaling is implicated in diseases such as cancer and fibrosis.
  • SMAD2 and SMAD3 are key transcription factors in TGF-β signaling, forming complexes with SMAD4 to regulate gene expression.

Purpose of the Study:

  • To elucidate the structural mechanisms underlying cofactor selection by SMAD2 and SMAD3.
  • To understand how cofactor interactions with SMAD proteins dictate TGF-β signaling output.

Main Methods:

  • Determined crystal structures of SMAD3 complexed with transcription factor FOXH1.
  • Determined crystal structures of SMAD2 complexed with transcriptional corepressor SKI.

Main Results:

  • The MAD homology 2 (MH2) domains of SMAD2 and SMAD3 possess multiple surface hydrophobic patches.
  • Cofactors interact with distinct subsets of these hydrophobic patches on SMAD proteins.
  • Cofactor binding can be cooperative or competitive, modulating TGF-β signaling outcomes.

Conclusions:

  • SMAD protein cofactor selection is mediated by specific interactions with surface hydrophobic patches on their MH2 domains.
  • The structural basis for cofactor selection provides insights into the precise control of TGF-β-dependent gene expression.
  • Understanding these interactions is crucial for deciphering disease mechanisms and developing therapeutic strategies for TGF-β-related disorders.

More Related Videos

Automated Hydrophobic Interaction Chromatography Column Selection for Use in Protein Purification10:21

Automated Hydrophobic Interaction Chromatography Column Selection for Use in Protein Purification

Published on: September 21, 2011

45.0K
Phthalic Acid Ester-Binding DNA Aptamer Selection, Characterization, and Application to an Electrochemical Aptasensor09:33

Phthalic Acid Ester-Binding DNA Aptamer Selection, Characterization, and Application to an Electrochemical Aptasensor

Published on: March 21, 2018

10.4K

Related Concept Videos

Cofactors and Coenzymes01:27

Cofactors and Coenzymes

Enzymes require additional components for proper function. There are two such classes of molecules: cofactors and coenzymes. Cofactors are metallic ions and coenzymes are non-protein organic molecules. Both of these types of helper molecule can be tightly bound to the enzyme or bound only when the substrate binds.
87.7K
Cofactors and Coenzymes01:24

Cofactors and Coenzymes

Enzymes are proteins made of amino acids. The functional group of each constituent amino acid catalyzes a wide variety of chemical reactions via ionic interactions or acid-base reactions. However, amino acids cannot catalyze oxidation-reduction and group transfer reactions and need to be aided by non-protein components called cofactors. Cofactors are also referred to as the chemical teeth of an enzyme.
Cofactors can be metallic ions or organic molecules called coenzymes. These types of helper...
12.8K
Protein-Drug Binding: Determination Methods01:22

Protein-Drug Binding: Determination Methods

Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
676
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...
5.2K
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...
15.2K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
8.0K