Characterizing the membrane recruitment domain of BDCPs and its role in gray platelet syndrome.

Authors

Anette Kathinka Dahl, Daniel Mann, Alf Håkon Lystad, Carsten Sachse, Anne Simonsen, Serhiy Pankiv

Published in

The Journal of cell biology. Volume 225. Issue 10. Oct 05, 2026. Epub Aug 06, 2026.

Abstract

BEACH domain-containing proteins (BDCPs) represent a family of large membrane-associated transmembrane cargo adaptors. In the current study, we determined the cryo-EM structure of the full-length typical BDCP NBEAL2, revealing an N-terminal arch-like structure with C-terminal globular domains attached to its convex surface. Using structure-guided deletion mutants and protein chimeras as well as native alternatively spliced isoforms and disease-related point mutants, we show that the N-terminal α-solenoid/concanavalin A-like domain assembly of the typical BDCPs NBEAL1, NBEAL2, LYST, ALFY, LRBA, and NBEA functions as a modular membrane recruitment domain. We report that gray platelet syndrome-associated single aa mutations L388P or E643V within the membrane recruitment domain of NBEAL2 disrupt its membrane targeting in stably transfected cells, highlighting a potential structure-function mechanism by which failed membrane recruitment cause gray platelet syndrome or other BDCPs-related diseases.

PMID:
42560489
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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