2X1P

Gelsolin Nanobody

Summary for 2X1P

• Entry DOI: 10.2210/pdb2x1p/pdb
• Related: 2X1O 2X1Q
• Descriptor: GELSOLIN NANOBODY (2 entities in total)
• Functional Keywords: contractile protein
• Biological source: LAMA GLAMA (LLAMA)
• Total number of polymer chains: 4
• Total formula weight: 54719.81

Authors

Van Den Abbeele, A.,Declercq, S.,De Ganck, A.,De Corte, V.,Van Loo, B.,Srinivasan, V.,Steyaert, J.,Van De Kerckhove, J.,Gettemans, J. (deposition date: 2010-01-03, release date: 2011-01-12, Last modification date: 2024-10-16)

Primary citation

Van Den Abbeele, A.,De Clercq, S.,De Ganck, A.,De Corte, V.,Van Loo, B.,Soror, S.H.,Srinivasan, V.,Steyaert, J.,Vandekerckhove, J.,Gettemans, J.
A Llama-Derived Gelsolin Single-Domain Antibody Blocks Gelsolin-G-Actin Interaction.
Cell.Mol.Life Sci., 67:1519-, 2010

PubMed Abstract: RNA interference has tremendously advanced our understanding of gene function but recent reports have exposed undesirable side-effects. Recombinant Camelid single-domain antibodies (VHHs) provide an attractive means for studying protein function without affecting gene expression. We raised VHHs against gelsolin (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin organization and migration. GsnVHH-induced delocalization of gelsolin to mitochondria or the nucleus in mammalian cells reveals distinct subpopulations including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13 specifically recognizes Ca(2+)-activated gelsolin (K (d) approximately 10 nM) while GsnVHH 11 binds gelsolin irrespective of Ca(2+) (K (d) approximately 5 nM) but completely blocks its interaction with G-actin. Both GsnVHHs trace gelsolin in membrane ruffles of EGF-stimulated MCF-7 cells and delay cell migration without affecting F-actin severing/capping or actin nucleation activities by gelsolin. We conclude that VHHs represent a potent way of blocking structural proteins and that actin nucleation by gelsolin is more complex than previously anticipated.

PubMed: 20140750
DOI: 10.1007/S00018-010-0266-1

Experimental method

X-RAY DIFFRACTION (1.1 Å)