10. Several types of molecules including the transmembrane glycoproteins can function as matrix receptors and co-receptors. However, the principal receptors on animal cells for binding most extracellular matrix proteins are the integrins.
    Which of the following statements is NOT true for integrins?
    (1) Integrins are transmembrane linker proteins that link to the cytoskeleton.
    (2) An integrin molecule is composed of two non- covalently associated glycoprotein subunits α and β. Both subunits span the cell membrane, with short intracellular C-terminal tails and large N-terminal extracellular domains.
    (3) The extracellular portion of the integrin dimer binds to specific carbohydrate
    residues in extracellular matrix proteins or to ligands on the surface of other cells.
    (4) The intracellular portion binds to a complex of proteins that form a linkage to the cytoskeleton.

Introduction: Integrin Basics

Integrins are the principal matrix receptors on animal cells, enabling communication and anchorage between the extracellular matrix (ECM) and the cell’s internal cytoskeleton. They serve as molecular bridges, regulating cell shape, mobility, proliferation, and survival.​

True Statements About Integrin Structure

• Statement (1): Integrins are transmembrane linker proteins connecting ECM to the cytoskeleton, mediating both physical and signaling interactions.​

• Statement (2): Integrin molecules consist of two non-covalently associated glycoprotein subunits, α and β, with each spanning the cell membrane and forming short intracellular tails and large extracellular domains.​

• Statement (4): The intracellular portion of integrins binds numerous adapter proteins, forming linkages to the cytoskeleton and assembling focal adhesions crucial for cell movement and signal transduction.​

The Incorrect Statement: Integrin Ligand Binding

Statement (3) is incorrect: The extracellular domains of integrins do NOT bind carbohydrate residues in ECM proteins. Instead, ligand recognition most commonly involves peptide sequences. For instance, integrins recognize the RGD tripeptide in fibronectin, as well as distinct regions in collagen and laminin. While some glycosylation may occur on ECM proteins, integrin specificity is based on the protein backbone rather than sugars.​

Integrin Binding Specificity

• Major ligands: Peptide motifs in ECM proteins (fibronectin, collagen, laminin).​

• Not carbohydrates: Integrins do not primarily interact with ECM protein sugar chains.​

• Integrin-ECM recognition: Driven by protein domains, not glycan residues.

Table: Integrin Structure and Function Analysis

Integrin Ligand Recognition

Integrin ligand recognition is:

• Highly specific to peptide sequences in ECM proteins (not sugars).​

• Essential for cell-ECM adhesion and cellular signaling.​

• Not related to carbohydrate binding; glycosylation of ECM proteins does not mediate integrin attachment.​

Conclusion

• Integrins are transmembrane heterodimers acting as principal matrix receptors, connecting cytoskeleton and ECM via protein domains.​

• The INCORRECT statement is that integrins bind carbohydrate residues on ECM proteins—their specificity is for peptide sequences, not glycan chains. This distinction is vital for understanding cell-matrix biology and integrin-targeted therapeutics.