How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs
KAUST DepartmentComputational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Biological and Environmental Sciences and Engineering (BESE) Division
MetadataShow full item record
AbstractLD motifs (leucine-aspartic acidmotifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs. © 2014 Biochemical Society.
SponsorsThis work was supported by funding from the King Abdullah University of Science and Technology (KAUST). T.A. was supported by a KAUST Baseline fund to Vladimir B. Bajic.
PublisherPortland Press Ltd.
- Molecular recognition of leucine-aspartate repeat (LD) motifs by the focal adhesion targeting homology domain of cerebral cavernous malformation 3 (CCM3).
- Authors: Li X, Ji W, Zhang R, Folta-Stogniew E, Min W, Boggon TJ
- Issue date: 2011 Jul 22
- Molecular recognition of paxillin LD motifs by the focal adhesion targeting domain.
- Authors: Hoellerer MK, Noble ME, Labesse G, Campbell ID, Werner JM, Arold ST
- Issue date: 2003 Oct
- Structural and mechanistic insights into the interaction between Pyk2 and paxillin LD motifs.
- Authors: Vanarotti MS, Miller DJ, Guibao CD, Nourse A, Zheng JJ
- Issue date: 2014 Dec 12
- Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats.
- Authors: Vanarotti MS, Finkelstein DB, Guibao CD, Nourse A, Miller DJ, Zheng JJ
- Issue date: 2016 Mar 8
- Structural analysis of the interactions between paxillin LD motifs and alpha-parvin.
- Authors: Lorenz S, Vakonakis I, Lowe ED, Campbell ID, Noble ME, Hoellerer MK
- Issue date: 2008 Oct 8