Aylwin C.Y. Ng
Human leucine-rich repeat proteins: A genome-wide bioinformatic categorization and functional analysis in innate immunity
Ng, Aylwin C.Y.; Eisenberg, Jason M.; Heath, Robert J.W.; Huett, Alan; Robinson, Cory M.; Nau, Gerard J.; Xavier, Ramnik J.
Authors
Jason M. Eisenberg
Robert J.W. Heath
ALAN HUETT Alan.Huett@nottingham.ac.uk
Assistant Professor
Cory M. Robinson
Gerard J. Nau
Ramnik J. Xavier
Abstract
In innate immune sensing, the detection of pathogen-associated molecular patterns by recognition receptors typically involve leucine-rich repeats (LRRs). We provide a categorization of 375 human LRR-containing proteins, almost half of which lack other identifiable functional domains. We clustered human LRR proteins by first assigning LRRs to LRR classes and then grouping the proteins based on these class assignments, revealing several of the resulting protein groups containing a large number of proteins with certain non-LRR functional domains. In particular, a statistically significantnumber of LRR proteins in the typical (T) and bacterial + typical (S+T) categories have transmembrane domains, whereas most of the LRR proteins in the cysteine-containing (CC) category contain an F-box domain (which mediates interactions with the E3 ubiquitin ligase complex). Furthermore, by examining the evolutionary profiles of the LRR proteins, we identified a subset of LRR proteins exhibiting strong conservation in fungi and an enrichment for "nucleic acid-binding" function. Expression analysis of LRR genes identifies a subset of pathogen-responsive genes in human primary macrophages infected with pathogenic bacteria. Using functional RNAi, we show that MFHAS1 regulates Toll-like receptor (TLR) - dependent signaling. By using protein interaction network analysis followed by functional RNAi, we identified LRSAM1 as a component of the antibacterial autophagic response.
Citation
Ng, A. C., Eisenberg, J. M., Heath, R. J., Huett, A., Robinson, C. M., Nau, G. J., & Xavier, R. J. (2011). Human leucine-rich repeat proteins: A genome-wide bioinformatic categorization and functional analysis in innate immunity. Proceedings of the National Academy of Sciences, 108(SUPPL. 1), 4631-4638. https://doi.org/10.1073/pnas.1000093107
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 11, 2010 |
Online Publication Date | Jun 29, 2010 |
Publication Date | Mar 15, 2011 |
Deposit Date | Aug 15, 2022 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Print ISSN | 0027-8424 |
Electronic ISSN | 1091-6490 |
Publisher | National Academy of Sciences |
Peer Reviewed | Peer Reviewed |
Volume | 108 |
Issue | SUPPL. 1 |
Pages | 4631-4638 |
DOI | https://doi.org/10.1073/pnas.1000093107 |
Public URL | https://nottingham-repository.worktribe.com/output/3181775 |
Publisher URL | https://www.pnas.org/doi/full/10.1073/pnas.1000093107 |
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