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Structure of adenov...
Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses
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Cupelli, Karolina (författare)
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Müller, Steffen (författare)
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Persson, David B (författare)
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Jost, Marco (författare)
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- Arnberg, Niklas (författare)
- Umeå universitet,Virologi,Molekylär Infektionsmedicin, Sverige (MIMS)
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Stehle, Thilo (författare)
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(creator_code:org_t)
- American Society for Microbiology, 2010
- 2010
- Engelska.
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 84:7, s. 3189-3200
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The complement regulation protein CD46 is the primary attachment receptor for most species B adenoviruses (Ads). However, significant variability exists in sequence and structure among species B Ads in the CD46-binding regions, correlating with differences in affinity. Here, we report a structure-function analysis of the interaction of the species B Ad21 knob with the two N-terminal repeats SCR1 and SCR2 of CD46, CD46-D2. We have determined the structures of the Ad21 knob in its unliganded form as well as in complex with CD46-D2, and we compare the interactions with those observed for the Ad11 knob-CD46-D2 complex. Surface plasmon resonance measurements demonstrate that the affinity of Ad21 knobs for CD46-D2 is 22-fold lower than that of the Ad11 knob. The superposition of the Ad21 and Ad11 knob structures in complex with CD46-D2 reveals a substantially different binding mode, providing an explanation for the weaker binding affinity of the Ad21 knob for its receptor. A critical difference in both complex structures is that a key interaction point, the DG loop, protrudes more in the Ad21 knob than in the Ad11 knob. Therefore, the protruding DG loop does not allow CD46-D2 to approach the core of the Ad21 knob as closely as in the Ad11 knob-CD46-D2 complex. In addition, the engagement of CD46-D2 induces a conformational change in the DG loop in the Ad21 knob but not in the Ad11 knob. Our results contribute to a more profound understanding of the CD46-binding mechanism of species B Ads and have relevance for the design of more efficient gene delivery vectors.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- bone-marrow transplantation
- cofactor protein CD46
- cellular receptor
- measles virus
- maximum likelihood
- crystal-structure
- fiber knob
- binding
- cells
- attachment
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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