5K6Z

Sidekick chimera containing sidekick-2 immunoglobulin domains 1-2 and sidekick-1 immunoglobulin domains 3-4

Summary for 5K6Z

• Entry DOI: 10.2210/pdb5k6z/pdb
• Related: 5K6U 5K6V 5K6W 5K6X 5K6Y 5K70
• Descriptor: Protein sidekick-2,Protein sidekick-1 chimera, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: cell adhesion, immunoglobulin
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q3UH53
• Total number of polymer chains: 2
• Total formula weight: 86718.77

Authors

Goodman, K.M.,Mannepalli, S.,Honig, B.,Shapiro, L. (deposition date: 2016-05-25, release date: 2016-09-28, Last modification date: 2020-07-29)

Primary citation

Goodman, K.M.,Yamagata, M.,Jin, X.,Mannepalli, S.,Katsamba, P.S.,Ahlsen, G.,Sergeeva, A.P.,Honig, B.,Sanes, J.R.,Shapiro, L.
Molecular basis of sidekick-mediated cell-cell adhesion and specificity.
Elife, 5:-, 2016

PubMed Abstract: Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1-4), arranged in a horseshoe conformation. These Ig1-4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions. Structure-guided mutagenesis results show that this canonical dimer is required for both Sdk-mediated cell aggregation (via interactions) and Sdk clustering in isolated cells (via interactions). Sdk1/Sdk2 recognition specificity is encoded across Ig1-4, with Ig1-2 conferring the majority of binding affinity and differential specificity. We suggest that competition between and interactions provides a novel mechanism to sharpen the specificity of cell-cell interactions.

PubMed: 27644106
DOI: 10.7554/eLife.19058

Experimental method

X-RAY DIFFRACTION (2.7 Å)