The EMILIN/Multimerin family
Alfonso Colombatti1, Paola Spessotto, Roberto Doliana
1Experimental Oncology 2, Centro di Riferimento Oncologico, Istituto di Ricerca e Cura a Carattere Scientifico Aviano, Italy. acolombatti@cro.it
Frontiers in Immunology
|May 9, 2012
Summary
The Elastin microfibrillar interface proteins (EMILINs) and Multimerins family, particularly EMILIN1, exhibit diverse functions. Their gC1q domain interacts with integrins, regulating cell proliferation and extracellular matrix roles.
Area of Science:
- Biochemistry and Molecular Biology
- Extracellular Matrix Research
- Cellular Signaling
Background:
- Elastin microfibrillar interface proteins (EMILINs) and Multimerins form a four-member family (EMILIN1, EMILIN2, Multimerin1, Multimerin2).
- These glycoproteins possess a unique N-terminus EMI domain and a C-terminus gC1q domain, characteristic of the gC1q/TNF superfamily.
- They assemble into homotrimeric, high molecular weight multimers predominantly found in the extracellular matrix.
Purpose of the Study:
- To review the diverse functions and domains of the EMILIN/Multimerin family.
- To emphasize the regulatory role of gC1q domain ligand-receptor interactions.
- To highlight unique structural and functional aspects of EMILIN1's gC1q domain.
Main Methods:
- Structural analysis of EMILIN1's gC1q domain using Nuclear Magnetic Resonance (NMR).
- Investigation of ligand-receptor interactions involving the gC1q domain and integrins (α4β1, α9β1).
- Assessment of cellular responses, including proliferation, following gC1q domain ligation.
Main Results:
- EMILIN1's gC1q domain exhibits a unique nine-stranded β-sandwich fold with a reduced trimeric contact surface.
- A highly dynamic protruding loop in the gC1q domain contains residue E933, a key interaction site for α4β1 and α9β1 integrins.
- Contrary to typical integrin interactions, gC1q ligation by integrins leads to reduced cell proliferation.
Conclusions:
- The EMILIN/Multimerin family plays multifaceted roles in cellular functions and extracellular matrix organization.
- The unique structure of EMILIN1's gC1q domain facilitates specific integrin interactions.
- Ligand-receptor interactions involving the gC1q domain can uniquely modulate cell proliferation, suggesting novel signaling pathways.
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