What question did this study set out to answer?

To characterize epitope binding, signaling, trafficking, and HIV-1 coreceptor activity using a novel panel of anti-CCR5 monoclonal antibodies.

February 1, 2002Molecular Biology of the CellOpen Access

Multiple Active States and Oligomerization of CCR5 Revealed by Functional Properties of Monoclonal Antibodies

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To characterize epitope binding, signaling, trafficking, and HIV-1 coreceptor activity using a novel panel of anti-CCR5 monoclonal antibodies.
Generated monoclonal antibodies against CCR5 (MC-1, MC-4, MC-5, MC-6, and MC-7) and mapped their epitope binding across receptor domains.
Assessed receptor activation, competition with natural chemokines (RANTES, MIP-1β) and HIV-1 Env, and receptor trafficking using flow cytometry and real-time confocal microscopy.
Analyzed receptor dimerization and internalization using energy transfer assays comparing bivalent antibodies with monovalent isoforms.
MC-1 targeted the second extracellular loop and promoted robust receptor endocytosis via energy transfer between CCR5 molecules, whereas its monovalent forms bound without inducing internalization.
MC-6 stabilized an active conformation across multiple domains, directly triggering intracellular signaling pathways.
MC-4 allowed RANTES binding and downstream signaling but selectively blocked agonist-mediated internalization, indicating distinct conformational states govern signaling and receptor endocytosis.

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Implication

In vitro study reveals diverse functional conformations and oligomer-driven internalization of CCR5, indicating distinct receptor activation pathways.

Cite This Study

Blanpain et al. (2002) studied this question.

synapsesocial.com/papers/6aac999be1bede24bd2238b0 https://doi.org/10.1091/mbc.01-03-0129

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Implication

In vitro study reveals diverse functional conformations and oligomer-driven internalization of CCR5, indicating distinct receptor activation pathways.

Multiple Active States and Oligomerization of CCR5 Revealed by Functional Properties of Monoclonal Antibodies

Key Points

Discussion

Implication

Cite This Study

Multiple Active States and Oligomerization of CCR5 Revealed by Functional Properties of Monoclonal Antibodies

Key Points

Discussion

Implication

Cite This Study

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