title: Molecular determinants for interaction of SHEP1 with Cas localize to a highly solvent-protected region in the complex.
abstract: Protein-protein interactions between SHEP and Cas proteins influence cellular signaling through tyrosine kinases, as well as integrin-mediated signaling, and may be linked to antiestrogen resistance. Data from past studies suggests that association between SHEP and Cas proteins is critical for these cellular effects. In this study, the interacting domains of each protein were co-expressed in bacteria and a soluble stable complex was purified. Deuterium exchange mass spectrometry was used to define regions that are buried when SHEP1 is in complex with Cas. The results reveal four segments in SHEP1 that are highly protected, including a region (residues 619-640) that contains a key residue, tyrosine 635, required for association with Cas. This region is predominately hydrophilic, yet remains protected from solvent in the complex.
authors.affiliation: Cancer Center, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Céline
authors.initials: C
authors.lastname: Derunes
authors.forename: Rosemary
authors.initials: R
authors.lastname: Burgess
authors.forename: Emilio
authors.initials: E
authors.lastname: Iraheta
authors.forename: Robert
authors.initials: R
authors.lastname: Kellerer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Becherer
authors.forename: Chris R
authors.initials: CR
authors.lastname: Gessner
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Krissi
authors.initials: K
authors.lastname: Hewitt
authors.forename: Kristiina
authors.initials: K
authors.lastname: Vuori
authors.forename: Elena B
authors.initials: EB
authors.lastname: Pasquale
authors.forename: Virgil L
authors.initials: VL
authors.lastname: Woods
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Ely
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D050719:Crk-Associated Substrate Protein / Q000737:chemistry* / Q000378:metabolism; D003903:Deuterium; D006801:Humans; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012997:Solvents / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; C405695:Sh2d3c protein, mouse; D012997:Solvents; D003903:Deuterium; D011505:Protein-Tyrosine Kinases