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Structure of adenovirus complexed with its internalization receptor, alphavbeta5 integrin
C Y Chiu1, P Mathias, G R Nemerow
1Department of Molecular and Medical Pharmacology, Crump Institute for Biological Imaging, University of California-Los Angeles School of Medicine, Los Angeles, California 90095, USA.
Journal of Virology
|July 10, 1999
Summary
Researchers used cryo-electron microscopy to visualize how human adenoviruses (Ad2 and Ad12) bind to integrin alphavbeta5, revealing structural details crucial for virus cell entry and internalization.
Area of Science:
- Structural biology
- Virology
- Biochemistry
Background:
- Integrin alphavbeta5 mediates adenovirus (Ad) cell entry.
- The penton base protein's RGD motif binds to integrins.
- Adenovirus type 12 (Ad12) RGD loop is less flexible than Ad2's, aiding structural studies.
Purpose of the Study:
- Determine the 3D structure of soluble integrin alphavbeta5 bound to Ad2 and Ad12.
- Elucidate the interaction mechanism between adenovirus and its integrin receptor.
- Understand how integrin binding facilitates virus entry.
Main Methods:
- Cryo-electron microscopy (cryo-EM) at ~21 Å resolution.
- Analysis of Ad2- and Ad12-integrin complexes.
- Kinetic analysis of Ad2-alphavbeta5 interactions.
Main Results:
- A ring of integrin density was observed above the penton base of both Ad2 and Ad12.
- Integrin density was more defined for Ad12 than Ad2, consistent with RGD loop flexibility.
- The integrin structure comprises a globular domain with an RGD-binding cleft and a distal domain with flexible tails.
- Approximately 4.2 integrin molecules bound per Ad2 penton base at saturation.
Conclusions:
- The structure reveals how integrin alphavbeta5 binds to adenovirus penton bases.
- Integrin clustering, promoted by the penton base RGD protrusions, is essential for virus internalization.
- These findings provide insights into the molecular mechanisms of adenovirus cell entry.