4yeq | pdb_00004yeq
L4b Domain of Human Laminin alpha-2
Structural highlights
DiseaseLAMA2_HUMAN Congenital muscular dystrophy type 1A. The disease is caused by mutations affecting the gene represented in this entry. FunctionLAMA2_HUMAN Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Publication Abstract from PubMedThe ~800 kD laminin heterotrimer forms a distinctive cross-shaped structure that further self-assembles into networks within the extracellular matrix (ECM). The domains at the laminin chain termini, which engage in network formation and cell-surface interaction, are well understood both structurally and functionally. In contrast, the structures and roles of additional domains embedded within the limbs of the laminin cross have remained obscure. Here we report the X-ray crystal structure, determined to 1.2 A resolution, of the human laminin alpha2 subunit L4b domain, site of an in-frame deletion mutation associated with mild congenital muscular dystrophy. The alpha2 L4b domain is an irregular beta-sandwich with many short and broken strands linked by extended loops. The most similar known structures are the carbohydrate-binding domains of bacterial cellulases, the ephrin binding domain of ephrin receptors, and MAM adhesion domains in various other eukaryotic cell-surface proteins. This similarity to mammalian adhesion modules, which was not predicted on the basis of amino acid sequence alone due to lack of detectable homology, suggests that laminin internal domains evolved from a progenitor adhesion molecule and may retain a role in cell adhesion in the context of the laminin trimer. This article is protected by copyright. All rights reserved. Laminin L4 Domain Structure Resembles Adhesion Modules in Ephrin Receptor and Other Transmembrane Glycoproteins.,Moran T, Gat Y, Fass D FEBS J. 2015 May 11. doi: 10.1111/febs.13319. PMID:25962468[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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