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Mapping of nanobody binding sites on human LRRK2 by CX-MS

ABSTRACT: As part of an in-depth characterization of nanobodies directed against the human Leucine-rich repeat kinase 2 (LRRK2), epitopes of the nanobodies bound to LRRK2 were mapped by chemical crosslinking combined with mass spectrometry using the CID-cleavable crosslinker disuccinimidyl sulfoxide (DSSO).

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Parkinson's Disease

SUBMITTER: Johannes Gloeckner

LAB HEAD: Christian Johannes Gloeckner

PROVIDER: PXD030063 | Pride | 2022-02-27

REPOSITORIES: Pride

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Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2.

Singh Ranjan K RK Soliman Ahmed A Guaitoli Giambattista G Störmer Eliza E von Zweydorf Felix F Dal Maso Thomas T Oun Asmaa A Van Rillaer Laura L Schmidt Sven H SH Chatterjee Deep D David Joshua A JA Pardon Els E Schwartz Thomas U TU Knapp Stefan S Kennedy Eileen J EJ Steyaert Jan J Herberg Friedrich W FW Kortholt Arjan A Gloeckner Christian Johannes CJ Versées Wim W

Proceedings of the National Academy of Sciences of the United States of America 20220301 9

Mutations in the gene coding for leucine-rich repeat kinase 2 (LRRK2) are a leading cause of the inherited form of Parkinson's disease (PD), while LRRK2 overactivation is also associated with the more common idiopathic form of PD. LRRK2 is a large multidomain protein, including a GTPase as well as a Ser/Thr protein kinase domain. Common, disease-causing mutations increase LRRK2 kinase activity, presenting LRRK2 as an attractive target for drug discovery. Currently, drug development has mainly fo ...[more]

PMID: 35217606

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