6DED

Crystal structure of the C-terminal ARM domain of Homo sapiens SPIN90 (SH3-protein interacting with Nck), residues 351-722

Summary for 6DED

• Entry DOI: 10.2210/pdb6ded/pdb
• Descriptor: NCK-interacting protein with SH3 domain (2 entities in total)
• Functional Keywords: inactive form, n-terminally truncated spin90, 6 and 2-3 armadillo repeats, unable to activate arp2-3 complex, endocytosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 84582.30

Authors

Nolen, B.J.,Luan, Q. (deposition date: 2018-05-11, release date: 2018-10-24, Last modification date: 2024-04-03)

Primary citation

Luan, Q.,Liu, S.L.,Helgeson, L.A.,Nolen, B.J.
Structure of the nucleation-promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex.
EMBO J., 37:-, 2018

PubMed Abstract: Unlike the WASP family of Arp2/3 complex activators, WISH/DIP/SPIN90 (WDS) family proteins activate actin filament nucleation by the Arp2/3 complex without the need for a preformed actin filament. This allows WDS proteins to initiate branched actin network assembly by providing seed filaments that activate WASP-bound Arp2/3 complex. Despite their important role in actin network initiation, it is unclear how WDS proteins drive the activating steps that require both WASP and pre-existing actin filaments during WASP-mediated nucleation. Here, we show that SPIN90 folds into an armadillo repeat domain that binds a surface of Arp2/3 complex distinct from the two WASP sites, straddling a hinge point that may stimulate movement of the Arp2 subunit into the activated short-pitch conformation. SPIN90 binds a surface on Arp2/3 complex that overlaps with actin filament binding, explaining how it could stimulate the same structural rearrangements in the complex as pre-existing actin filaments. By revealing how WDS proteins activate the Arp2/3 complex, these data provide a molecular foundation to understand initiation of dendritic actin networks and regulation of Arp2/3 complex by its activators.

PubMed: 30322896
DOI: 10.15252/embj.2018100005

Experimental method

X-RAY DIFFRACTION (2.204 Å)