This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Peptidoglycan recognition proteins (PGRPs) are pattern recognition molecules of the innate immune system that bind and, in certain cases, hydrolyze peptidoglycans (PGNs) of bacterial cell walls (1). They are highly conserved from insects to mammals. PGRPs bind PGNs with high affinity and are important contributors to host defense against bacterial infections. Insects PGRPs, of which there are at least 19, are involved in activating signaling pathways that induce expression of anti-microbial peptides. By contrast, mammalian PGRPs, of which there are four, do not act through host signaling pathways, but are directly bactericidal against both Gram-positive and -negative bacteria (1). Indeed, these PGRPs are a new class of bactericidal proteins that have a different structure and mechanism of action than currently known mammalian antimicrobial peptides. Mammalian PGRP-L is an N-acetylmuramoyl-L-alanine amidase that hydrolyzes PGN. Very recently, it was found that PGRP-L also has a proinflammatory function, unrelated to its amidase activity (2). We previously published structures of human PGRP-Ialpha and -Ibeta in complex with PGN fragments, and have proposed a mechanism for their bactericidal activity (3,4). We now plan to extend our work to PGRP-L, which contains a large N-terminal domain with no sequence homology to other known proteins, and whose structure remains to be established. The PGRP-L structure will provide insights into how three different types of pattern recognition molecules (PGRPs, Nod2 and TLR4) play interdependent roles in inflammatory responses to bacterial pathogens. Recently, We obtained a few small crystals which are too small (~50um) for data collection with our in-house detector. They diffract to a maximum resolution of 7 ? with unit cell dimensions of

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-27
Application #
7955594
Study Section
Special Emphasis Panel (ZRG1-BCMB-E (40))
Project Start
2009-07-01
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
27
Fiscal Year
2009
Total Cost
$11,653
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Kozlov, Guennadi; Wong, Kathy; Gehring, Kalle (2018) Crystal structure of the Legionella effector Lem22. Proteins 86:263-267
Ménade, Marie; Kozlov, Guennadi; Trempe, Jean-François et al. (2018) Structures of ubiquitin-like (Ubl) and Hsp90-like domains of sacsin provide insight into pathological mutations. J Biol Chem 293:12832-12842
Xu, Jie; Kozlov, Guennadi; McPherson, Peter S et al. (2018) A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds actin and is required for autophagy. J Biol Chem 293:4566-4574
Dean, Dexter N; Rana, Pratip; Campbell, Ryan P et al. (2018) Propagation of an A? Dodecamer Strain Involves a Three-Step Mechanism and a Key Intermediate. Biophys J 114:539-549
Chen, Yu Seby; Kozlov, Guennadi; Fakih, Rayan et al. (2018) The cyclic nucleotide-binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg2+ efflux activity. J Biol Chem 293:19998-20007
Xu, Caishuang; Kozlov, Guennadi; Wong, Kathy et al. (2016) Crystal Structure of the Salmonella Typhimurium Effector GtgE. PLoS One 11:e0166643
Cogliati, Massimo; Zani, Alberto; Rickerts, Volker et al. (2016) Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population. Fungal Genet Biol 87:22-9
Oot, Rebecca A; Kane, Patricia M; Berry, Edward A et al. (2016) Crystal structure of yeast V1-ATPase in the autoinhibited state. EMBO J 35:1694-706
Lucido, Michael J; Orlando, Benjamin J; Vecchio, Alex J et al. (2016) Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. Biochemistry 55:1226-38
Bauman, Joseph D; Harrison, Jerry Joe E K; Arnold, Eddy (2016) Rapid experimental SAD phasing and hot-spot identification with halogenated fragments. IUCrJ 3:51-60

Showing the most recent 10 out of 375 publications