PDBsum entry 1q5c

Structural protein

PDB id

1q5c

Contents

			Protein chains

					540 a.a. *

			Ligands

					NAG ×52


					NDG ×8

			Metals

					_CA ×48

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Untangling desmosomal knots with electron tomography.

Authors

W.He, P.Cowin, D.L.Stokes.

Ref.

Science, 2003, 302, 109-113. [DOI no: 10.1126/science.1086957]

PubMed id

14526082

Abstract

Cell adhesion by adherens junctions and desmosomes relies on interactions between cadherin molecules. However, the molecular interfaces that define molecular specificity and that mediate adhesion remain controversial. We used electron tomography of plastic sections from neonatal mouse skin to visualize the organization of desmosomes in situ. The resulting three-dimensional maps reveal individual cadherin molecules forming discrete groups and interacting through their tips. Fitting of an x-ray crystal structure for C-cadherin to these maps is consistent with a flexible intermolecular interface mediated by an exchange of amino-terminal tryptophans. This flexibility suggests a novel mechanism for generating both cis and trans interactions and for propagating these adhesive interactions along the junction.



	Figure 1. Fig. 1. Images of desmosomes from neonatal mouse epidermis. (A) Low-magnification image showing an irregular border between keratinocytes coupled by frequent desmosomes. This region of the cell contains many ribosomes but, if the opaque discs are construed as en face views of desmosomes, lacks organelles. (B to D) Higher magnification images reveal the typical lamellar structure of desmosomes. The membrane appears as a narrow white zone; cadherin molecules appear as strands crossing the extracellular space, which is bisected by an electron-dense midline. Individual cadherins are difficult to identify because of extensive superposition of these densely packed molecules within the section; individual molecules are more readily seen in ultrathin sections that are unsuitable for tomography but are included in (13). A very dense plaque abuts the intracellular face of the membrane and leads to a looser network of fibrous densities that ultimately connect to bundles of intermediate filaments. (E and F) Sections through the tomographic reconstruction of desmosome "R" (see Table 1) cut parallel (E) and perpendicular (F) to the untilted sample [e.g., (B)]. The membrane is outlined in red, cadherin molecules in blue, two zones of the cytoplasmic plaque in orange and light green, and intermediate filaments in dark green. The perpendicular section in (F) reveals the thickness of the plastic section and illustrates that the resolution was quite isotropic [see also (13)]. Scale bars, 500 nm (A), 100 nm [(B) to (D)], 30 nm [(E) and (F)].		Figure 2. Fig. 2. Delineation and fitting of cadherin molecules to the desmosome. With the C-cadherin x-ray structure as a template, 136 cadherin molecules were delineated in the region of desmosome "P" (see Table 1). (A) Densities from the map, with individual cadherin molecules in various colors and the membrane in cyan. (B) A representative group of cadherin molecules clustering at the midline and interacting predominantly at their tips. (C to E) Three recurrent molecular interactions within the molecular groups, referred to as W, S, and , respectively. The x-ray structure for C-cadherin was fitted as a rigid body with no changes within the structure itself. (G to I) The resulting juxtaposition of EC1 domains, where each molecule has a distinct ribbon color, calcium ions are brown, the space-filling representation of the Trp2 side chain is dark orange, and the HAV sequence has a light orange ribbon with stick-like side chains.

PROCHECK

	Headers