Article
- The EMBO Journal (2002) 21, 4785 - 4795
- doi:10.1093/emboj/cdf502
Subject Categories:
Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain
Gerwald Jogl1, Yang Shen1, Damara Gebauer1, Jiang Li1, Katja Wiegmann2, Hamid Kashkar2, Martin Krönke2 and Liang Tong1
- Department of Biological Sciences, Columbia University, New York, NY 10027, USA
- Institute of Medical Microbiology, Immunology and Hygiene, University of Cologne, D-50935 Köln, Germany
Correspondence to:
Liang Tong, E-mail: tong@como.bio.columbia.edu
Received 17 May 2002; Accepted 31 July 2002; Revised 23 July 2002
Abstract
The BEACH domain is highly conserved in a large family of eukaryotic proteins, and is crucial for their functions in vesicle trafficking, membrane dynamics and receptor signaling. However, it does not share any sequence homology with other proteins. Here we report the crystal structure at 2.9 Å resolution of the BEACH domain of human neurobeachin. It shows that the BEACH domain has a new and unusual polypeptide backbone fold, as the peptide segments in its core do not assume regular secondary structures. Unexpectedly, the structure also reveals that the BEACH domain is in extensive association with a novel, weakly conserved pleckstrin-homology (PH) domain. Consistent with the structural analysis, biochemical studies show that the PH and BEACH domains have strong interactions, suggesting they may function as a single unit. Functional studies in intact cells demonstrate the requirement of both the PH and the BEACH domains for activity. A prominent groove at the interface between the two domains may be used to recruit their binding partners.
Keywords:
- Chediak–Higashi syndrome,
- protein structure,
- TNF signaling,
- vesicle trafficking
