Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...

You might also read

Related Articles

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

Sort by
Same author

The β<sub>8</sub> integrin EGF domains support a constitutive extended conformation, and the cytoplasmic domain impairs outside-in signaling.

Journal of cellular physiology·2022
Same author

Effects of the association of the α<sub>v</sub> β<sub>8</sub> lower legs on integrin ligand binding.

Journal of cellular biochemistry·2021
Same author

Atypical structure and function of integrin α<sub>V</sub> β<sub>8</sub>.

Journal of cellular physiology·2020
Same author

The interface between the EGF1 and EGF2 domains is critical in integrin affinity regulation.

Journal of cellular biochemistry·2018
Same author

Structural basis of antifreeze activity of a bacterial multi-domain antifreeze protein.

PloS one·2017
Same author

Recrystallization inhibition in ice due to ice binding protein activity detected by nuclear magnetic resonance.

Biotechnology reports (Amsterdam, Netherlands)·2017

Related Experiment Video

Updated: Jun 27, 2026

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs
04:15

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs

Published on: February 2, 2024

Rationally designed integrin beta3 mutants stabilized in the high affinity conformation.

Bing-Hao Luo1, John Karanicolas, Laura D Harmacek

  • 1Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

The Journal of Biological Chemistry
|November 21, 2008
PubMed
Summary

Researchers identified key amino acid side chains influencing integrin alphaIIbbeta3 conformation. This understanding aids developing targeted allosteric drugs for cell signaling modulation.

More Related Videos

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
07:22

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)

Published on: January 12, 2024

Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies
13:52

Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies

Published on: March 19, 2014

Related Experiment Videos

Last Updated: Jun 27, 2026

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs
04:15

A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs

Published on: February 2, 2024

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
07:22

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)

Published on: January 12, 2024

Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies
13:52

Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies

Published on: March 19, 2014

Area of Science:

  • Biochemistry
  • Cell Biology
  • Structural Biology

Background:

  • Integrins are crucial cell surface receptors mediating bidirectional signaling.
  • Conformational changes in integrin beta-subunit headpieces regulate ligand binding and function.
  • Previous methods for inducing integrin conformations were coarse.

Purpose of the Study:

  • To achieve a detailed understanding of integrin conformational changes.
  • To identify specific amino acid residues critical for the balance between open and closed integrin conformations.
  • To explore the propagation of conformational changes within the integrin structure.

Main Methods:

  • Utilized computational design techniques to identify key amino acid side chains.
  • Designed eight single-point mutants at selected sites within alphaIIbbeta3.
  • Analyzed ligand binding affinity and conformational extension of the mutants.

Main Results:

  • Identified five amino acid side chains critical for the energetic balance of alphaIIbbeta3 conformations.
  • Five single-point mutants exhibited significantly enhanced ligand binding compared to wild type.
  • Mutant integrins displayed a more extended conformation, indicating propagated changes.

Conclusions:

  • Detailed understanding of alphaIIbbeta3 conformational dynamics was achieved.
  • Computational design successfully identified key residues modulating integrin conformation and function.
  • Findings facilitate the development of allosteric drugs targeting specific integrin states.