title: Structure of an asymmetric ternary protein complex provides insight for membrane interaction.
abstract: Plasma membrane repair involves the coordinated effort of proteins and the inner phospholipid surface to mend the rupture and return the cell back to homeostasis. Here, we present the three-dimensional structure of a multiprotein complex that includes S100A10, annexin A2, and AHNAK, which along with dysferlin, functions in muscle and cardiac tissue repair. The 3.5 Å resolution X-ray structure shows that a single region from the AHNAK C terminus is recruited by an S100A10-annexin A2 heterotetramer, forming an asymmetric ternary complex. The AHNAK peptide adopts a coil conformation that arches across the heterotetramer contacting both annexin A2 and S100A10 protomers with tight affinity (∼30 nM) and establishing a structural rationale whereby both S100A10 and annexin proteins are needed in AHNAK recruitment. The structure evokes a model whereby AHNAK is targeted to the membrane surface through sandwiching of the binding region between the S100A10/annexin A2 complex and the phospholipid membrane.
authors.affiliation: Department of Biochemistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Dempsey
authors.forename: Atoosa
authors.initials: A
authors.lastname: Rezvanpour
authors.forename: Ting-Wai
authors.initials: TW
authors.lastname: Lee
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Barber
authors.forename: Murray S
authors.initials: MS
authors.lastname: Junop
authors.forename: Gary S
authors.initials: GS
authors.lastname: Shaw
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017306:Annexin A2 / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D009418:S100 Proteins / Q000737:chemistry*; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C075176:AHNAK protein, human; C472822:ANXA2 protein, human