4DRW

Crystal Structure of the Ternary Complex between S100A10, an Annexin A2 N-terminal Peptide and an AHNAK Peptide

Summary for 4DRW

• Entry DOI: 10.2210/pdb4drw/pdb
• Descriptor: Protein S100-A10/Annexin A2 chimeric protein, Neuroblast differentiation-associated protein AHNAK (2 entities in total)
• Functional Keywords: atypical ef-hand, heteropentameric complex, membrane repair, exocytosis-protein binding complex, exocytosis/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space, extracellular matrix, basement membrane : P07355; Nucleus: Q09666
• Total number of polymer chains: 6
• Total formula weight: 59696.76

Authors

Rezvanpour, A.,Lee, T.-W.,Junop, M.S.,Shaw, G.S. (deposition date: 2012-02-17, release date: 2012-10-24, Last modification date: 2024-11-27)

Primary citation

Dempsey, B.R.,Rezvanpour, A.,Lee, T.W.,Barber, K.R.,Junop, M.S.,Shaw, G.S.
Structure of an asymmetric ternary protein complex provides insight for membrane interaction.
Structure, 20:1737-1745, 2012

PubMed 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.

PubMed: 22940583
DOI: 10.1016/j.str.2012.08.004

Experimental method

X-RAY DIFFRACTION (3.5 Å)