Related Experiment Video

Updated: Feb 27, 2026

Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
10:24

Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry

Published on: June 7, 2018

9.3K

Biochemical characterization of functional domains of the chaperone Cosmc

Melinda S Hanes1, Kelley W Moremen2, Richard D Cummings1

  • 1Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

Plos One
|July 1, 2017
PubMed

Insights

Cosmc chaperone protein structure was investigated, revealing its N-terminal domain mediates T-synthase binding and function, while the C-terminal domain is crucial for oligomerization and metal binding.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Glycobiology

Background:

  • Cosmc is an endoplasmic reticulum chaperone essential for O-GalNAc glycosylation.
  • Loss-of-function mutations in Cosmc lead to Tn antigen expression, linked to cancer.
  • The structure-function relationship of Cosmc remains poorly understood.

Purpose of the Study:

  • To elucidate the domain organization, oligomerization, and cofactor interactions of Cosmc.
  • To understand how Cosmc mutations affect its structure and chaperone activity.
  • To provide insights into the regulation of Cosmc's in vivo function.

Main Methods:

  • Limited proteolysis to identify structured domains.
  • Chemical crosslinking and blue native PAGE to assess oligomerization.
  • Thermal shift assays to investigate metal ion binding.

Main Results:

  • Cosmc possesses a structured N-terminal domain (CosmcΔ256) retaining chaperone activity.
  • The N-terminal domain mediates T-synthase binding and chaperone function.
  • The C-terminal domain is essential for Cosmc oligomerization and divalent cation binding.
  • A loss-of-function mutation (CosmcE152K) affects metal binding and oligomerization but not in vitro activity.

Conclusions:

  • Cosmc functions as a modular protein with distinct domains for T-synthase interaction and oligomerization/metal binding.
  • The N-terminal domain is critical for chaperone activity, while the C-terminal domain regulates oligomerization and metal coordination.
  • These findings offer new structure-function insights into Cosmc and suggest regulatory mechanisms for its in vivo activity.

More Related Videos

Identification of Functional Protein Regions Through Chimeric Protein Construction11:39

Identification of Functional Protein Regions Through Chimeric Protein Construction

Published on: January 8, 2019

11.0K
High-Resolution Complexome Profiling by Cryoslicing BN-MS Analysis09:33

High-Resolution Complexome Profiling by Cryoslicing BN-MS Analysis

Published on: October 15, 2019

7.8K

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

15.2K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
20.5K
Conservation of Protein Domains Over Different Proteins02:26

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...
14.8K
Mechanical Protein Function01:58

Mechanical Protein Function

2.6K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
632