title: Tandem SAM domain structure of human Caskin1: a presynaptic, self-assembling scaffold for CASK.
abstract: The synaptic scaffolding proteins CASK and Caskin1 are part of the fibrous mesh of proteins that organize the active zones of neural synapses. CASK binds to a region of Caskin1 called the CASK interaction domain (CID). Adjacent to the CID, Caskin1 contains two tandem sterile α motif (SAM) domains. Many SAM domains form polymers so they are good candidates for forming the fibrous structures seen in the active zone. We show here that the SAM domains of Caskin1 form a new type of SAM helical polymer. The Caskin1 polymer interface exhibits a remarkable segregation of charged residues, resulting in a high sensitivity to ionic strength in vitro. The Caskin1 polymers can be decorated with CASK proteins, illustrating how these proteins may work together to organize the cytomatrix in active zones.
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-DOE Institute of Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1570, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Stafford
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hinde
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Knight
authors.forename: Mario A
authors.initials: MA
authors.lastname: Pennella
authors.forename: Jason
authors.initials: J
authors.lastname: Ear
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Digman
authors.forename: Enrico
authors.initials: E
authors.lastname: Gratton
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D051528:Guanylate Kinases / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D013569:Synapses / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C473247:CASKIN1 protein, human; D009419:Nerve Tissue Proteins; C106868:CASK kinases; D051528:Guanylate Kinases