Structural highlights
Disease
[SPN90_HUMAN] A chromosomal aberration involving NCKIPSD/AF3p21 is found in therapy-related leukemia. Translocation t(3;11)(p21;q23) with KMT2A/MLL1.[1]
Function
[SPN90_HUMAN] Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1). Induces microspike formation, in vivo (By similarity). In vitro, stimulates N-WASP-induced ARP2/3 complex activation in the absence of CDC42 (By similarity). May play an important role in the maintenance of sarcomeres and/or in the assembly of myofibrils into sarcomeres. Implicated in regulation of actin polymerization and cell adhesion. Plays a role in angiogenesis.[2]
Publication Abstract from PubMed
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.
Structure of the nucleation-promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex.,Luan Q, Liu SL, Helgeson LA, Nolen BJ EMBO J. 2018 Oct 15. pii: embj.2018100005. doi: 10.15252/embj.2018100005. PMID:30322896[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sano K, Hayakawa A, Piao JH, Kosaka Y, Nakamura H. Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23). Blood. 2000 Feb 1;95(3):1066-8. PMID:10648423
- ↑ Rahimi N, Rezazadeh K, Mahoney JE, Hartsough E, Meyer RD. Identification of IGPR-1 as a novel adhesion molecule involved in angiogenesis. Mol Biol Cell. 2012 May;23(9):1646-56. doi: 10.1091/mbc.E11-11-0934. Epub 2012, Mar 14. PMID:22419821 doi:http://dx.doi.org/10.1091/mbc.E11-11-0934
- ↑ Luan Q, Liu SL, Helgeson LA, Nolen BJ. Structure of the nucleation-promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex. EMBO J. 2018 Oct 15. pii: embj.2018100005. doi: 10.15252/embj.2018100005. PMID:30322896 doi:http://dx.doi.org/10.15252/embj.2018100005
