4F14

Structure of the SH3 domain of human nebulette in complex with a peptide of XIRP2

Summary for 4F14

• Entry DOI: 10.2210/pdb4f14/pdb
• Descriptor: Nebulette, Xin actin-binding repeat-containing protein 2, ZINC ION, ... (4 entities in total)
• Functional Keywords: sh3 domain, heart muscle, actin-binding protein-peptide complex, actin-binding protein/peptide
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 2: Cytoplasm : O76041; Cell junction : A4UGR9
• Total number of polymer chains: 2
• Total formula weight: 8873.28

Authors

Sauer, F.,Vahokoski, J.,Wilmanns, M. (deposition date: 2012-05-06, release date: 2012-06-20, Last modification date: 2024-02-28)

Primary citation

Eulitz, S.,Sauer, F.,Pelissier, M.C.,Boisguerin, P.,Molt, S.,Schuld, J.,Orfanos, Z.,Kley, R.A.,Volkmer, R.,Wilmanns, M.,Kirfel, G.,van der Ven, P.F.,Furst, D.O.
Identification of Xin-repeat proteins as novel ligands of the SH3 domains of nebulin and nebulette and analysis of their interaction during myofibril formation and remodeling.
Mol Biol Cell, 24:3215-3226, 2013

PubMed Abstract: The Xin actin-binding repeat-containing proteins Xin and XIRP2 are exclusively expressed in striated muscle cells, where they are believed to play an important role in development. In adult muscle, both proteins are concentrated at attachment sites of myofibrils to the membrane. In contrast, during development they are localized to immature myofibrils together with their binding partner, filamin C, indicating an involvement of both proteins in myofibril assembly. We identify the SH3 domains of nebulin and nebulette as novel ligands of proline-rich regions of Xin and XIRP2. Precise binding motifs are mapped and shown to bind both SH3 domains with micromolar affinity. Cocrystallization of the nebulette SH3 domain with the interacting XIRP2 peptide PPPTLPKPKLPKH reveals selective interactions that conform to class II SH3 domain-binding peptides. Bimolecular fluorescence complementation experiments in cultured muscle cells indicate a temporally restricted interaction of Xin-repeat proteins with nebulin/nebulette during early stages of myofibril development that is lost upon further maturation. In mature myofibrils, this interaction is limited to longitudinally oriented structures associated with myofibril development and remodeling. These data provide new insights into the role of Xin actin-binding repeat-containing proteins (together with their interaction partners) in myofibril assembly and after muscle damage.

PubMed: 23985323
DOI: 10.1091/mbc.E13-04-0202

Experimental method

X-RAY DIFFRACTION (1.2 Å)