title: Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain.
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 A 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.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Gerwald
authors.initials: G
authors.lastname: Jogl
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Damara
authors.initials: D
authors.lastname: Gebauer
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Katja
authors.initials: K
authors.lastname: Wiegmann
authors.forename: Hamid
authors.initials: H
authors.lastname: Kashkar
authors.forename: Martin
authors.initials: M
authors.lastname: Krönke
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002609:Chediak-Higashi Syndrome / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C498595:NBEA protein, human; C102036:NSMAF protein, human; C403265:Nbea protein, mouse; D009419:Nerve Tissue Proteins; C491112:Nsmaf protein, mouse; D011506:Proteins; D011993:Recombinant Fusion Proteins