The BEACH Domain Project

BEACH domains are highly conserved in a large family of eukaryotic proteins that are involved in vesicle trafficking, membrane dynamics, cytokinesis, and receptor signaling.

The BEACH domain was first identified in the proteins beige and CHS. Chediak-Higashi Syndrome (CHS) is a rare, autosomal recessive disorder that can cause severe immunodeficiency and albinism in humans. Unless treated by bone marrow transplantation, CHS patients generally die in childhood. beige is the name for CHS disease in mice and other animals.

BEACH domains share no detectable sequence homology with other proteins in the database. Its exact biochemical/biological function is currently not known. BEACH-containing proteins are generally very large, from 900 residues for the protein FAN to 3800 residues for CHS.

Major findings from this project

The crystal structure of the BEACH domain of human neurobeachin has been determined at 2.9A resolution.

The BEACH domain has a novel and unusual fold. Several polypeptide segments in the core of the domain do not assume regular secondary structures.

A novel PH domain just prior to the BEACH domain in the amino acid sequence was revealed from the structural studies.
There is an extensive interface between the PH and BEACH domains, and the affinity between the two domains have been estimated to be around 1 uM based on GST pull-down experiments.
The BEACH and PH domains may function as a single unit.

Publications from this project

G. Jogl, Y. Shen, D. Gebauer, J. Li, K. Wiegmann, H. Kashkar, M. Kronke & L. Tong. (2002). Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain. EMBO J. 21, 4785-4795.
D. Gebauer,* J. Li,* G. Jogl, Y. Shen, D.G. Myszka & L. Tong. (2004). Crystal structure of the PH-BEACH domains of human LRBA/BGL. Biochem. 43, 14873-14880. (*-equal first authors)

Funding for this project

NIH R01 GM66753