Research Topics
Genomes and Genes
| M A ArnaoutSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Molecular genetics and pathogenesis of autosomal dominant polycystic kidney diseaseM A Arnaout
Renal Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
Annu Rev Med 52:93-123. 2001....
Structure and mechanics of integrin-based cell adhesionM Amin Arnaout
Nephrology Division, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, United States
Curr Opin Cell Biol 19:495-507. 2007..Recent advances in the structural elucidation of integrins and integrin-binding cytoskeleton proteins are the subjects of this review...- Integrin structure, allostery, and bidirectional signalingM A Arnaout
Structural Biology Program, Leukocyte Biology and Inflammation Program, Nephrology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachussetts 02129, USA
Annu Rev Cell Dev Biol 21:381-410. 2005..Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions... - Coming to grips with integrin binding to ligandsM Amin Arnaout
Renal Unit, Leukocyte Biology and Inflammation Program, Massachusetts General Hospital, and Harvard Medical School, Charlestown, MA 02129, USA
Curr Opin Cell Biol 14:641-51. 2002..These models provide new insights into the molecular basis for ligand binding specificity in integrins and its regulation by activation-driven tertiary and quaternary changes... - Integrin structure: new twists and turns in dynamic cell adhesionM Amin Arnaout
Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Immunol Rev 186:125-40. 2002..These findings provide the framework for new investigations of structure-activity relationships in integrins, with important implications for targeting these receptors therapeutically [corrected]... - Crystal structure of the extracellular segment of integrin alpha Vbeta3J P Xiong
Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
Science 294:339-45. 2001..MIDAS lies adjacent to a calcium-binding site with a potential regulatory function... - Integrins, cations and ligands: making the connectionJ-P Xiong
Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, Charlestown, MA 02129, USA
J Thromb Haemost 1:1642-54. 2003.... - Expression of a soluble and functional form of the human beta 2 integrin CD11b/CD18N Dana
Renal Unit, Massachusetts General Hospital, Boston, MA
Proc Natl Acad Sci U S A 88:3106-10. 1991..The secreted receptor exhibited direct and specific binding to its ligand, iC3b, the major complement C3 opsonin, and inhibited binding of polymorphonuclear cells to recombinant interleukin 1-activated endothelium... - The zinc finger transcription factor ZBP-89 is a repressor of the human beta 2-integrin CD11b geneHeiyoung Park
Leukocyte Biology and Inflammation Program, Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Blood 101:894-902. 2003..A clear inverse relationship was observed in the latter but not the former state, suggesting that ZBP-89 represses CD11b gene expression during the further differentiation of monocytes into macrophages... - Two conformations of the integrin A-domain (I-domain): a pathway for activation?J O Lee
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Structure 3:1333-40. 1995.... - Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligandJian Ping Xiong
Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA
Science 296:151-5. 2002..Ligand binding induces small changes in the orientation of alphaV relative to beta3... - New insights into the structural basis of integrin activationJian-Ping Xiong
Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, and Harvard Medical School, Charlestown, MA 02129, USA
Blood 102:1155-9. 2003..In this perspective, we develop a new hypothesis for integrin activation based on recent crystallographic, electron microscopic, and biochemical studies... - The beta-tail domain (betaTD) regulates physiologic ligand binding to integrin CD11b/CD18Vineet Gupta
Nephrology Division, Leukocyte Biology and Inflammation Program, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
Blood 109:3513-20. 2007..These data identify a role for the membrane proximal betaTD as an allosteric modulator of integrin activation... - A novel adaptation of the integrin PSI domain revealed from its crystal structureJian Ping Xiong
Structural Biology Program, Leukocyte Biology and Inflammation Program, Renal Unit
J Biol Chem 279:40252-4. 2004..This architecture may be relevant to the evolution of integrins and should help refine the current models of integrin activation... - Polycystin-1 interacts with intermediate filamentsG M Xu
Renal Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Biol Chem 276:46544-52. 2001..Polycystin-1 may utilize this association for structural, storage, or signaling functions... - Mapping of the human CD11c (ITGAX) and CD11d (ITGAD) genes demonstrates that they are arranged in tandem separated by no more than 11.5 kbC S Shelley
Leukocyte Biology and Inflammation Program, Massachusetts General Hospital, Harvard Medical School, Boston 02115, USA
Genomics 49:334-6. 1998 - During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoterC Simon Shelley
Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
J Immunol 168:3887-93. 2002..Together, these increases in the functional activity of both Puralpha and Sp1 combine to induce CD11c expression... - Crystal structure of the complete integrin alphaVbeta3 ectodomain plus an alpha/beta transmembrane fragmentJian Ping Xiong
Program in Leukocyte Biology and Inflammation, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
J Cell Biol 186:589-600. 2009.... - WAC, a novel WW domain-containing adapter with a coiled-coil region, is colocalized with splicing factor SC35G Mark Xu
Polycystic Kidney Disease Program, Renal Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Genomics 79:87-94. 2002..Immunofluorescence analysis colocalized WAC with SC35, the marker for pre-mRNA splicing machinery. Our analysis suggests that WAC represents a novel member of WW-domain-containing proteins for RNA processing... - The human beta 2 integrin CD18 promoter consists of two inverted Ets cis elementsE P Bottinger
Department of Medicine, Harvard Medical School, Charlestown, Massachusetts
Mol Cell Biol 14:2604-15. 1994.... - Polycystin 1 is required for the structural integrity of blood vesselsK Kim
Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 97:1731-6. 2000..These data reveal a requisite role for polycystin 1 in maintaining the structural integrity of the vasculature as well as epithelium and suggest that the nature of the PKD1 mutation contributes to the phenotypic variance in ADPKD... - Characterization of a conformationally sensitive murine monoclonal antibody directed to the metal ion-dependent adhesion site face of integrin CD11bRui Li
Leukocyte Biology and Inflammation Program, Structural Biology Program, Renal Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
J Immunol 168:1219-25. 2002..These data support a functional relevance of the protein movements on the MIDAS face and suggest that stabilizing the A domain in the low-affinity state may have therapeutic benefit... - Role of the beta-subunit arginine/lysine finger in integrin heterodimer formation and functionVineet Gupta
Division of Nephrology, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
J Immunol 180:1713-8. 2008..These data demonstrate an important role of the Arg/Lys finger in formation of a stable integrin heterodimer, and suggest that subtle changes at this residue affect the activation state of the integrin... - A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand bindingM Michishita
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129
Cell 72:857-67. 1993.... - Anti-PR3 immune responses induce segmental and necrotizing glomerulonephritisV C Primo
The Nephrology Division, Massachusetts General Hospital Harvard Medical School, Boston, MA 02129, USA
Clin Exp Immunol 159:327-37. 2010.... - Divergent response to LPS and bacteria in CD14-deficient murine macrophagesK J Moore
Lipid Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
J Immunol 165:4272-80. 2000..coli. These data indicate that CD14 is essential for macrophage responses to free LPS, whereas other receptors, including CD11b/CD18, can compensate for the loss of CD14 in response to whole bacteria... - A simple, no-wash cell adhesion-based high-throughput assay for the discovery of small-molecule regulators of the integrin CD11b/CD18Jun Y Park
Nephrology Division, Leukocyte Biology and Inflammation Program, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
J Biomol Screen 12:406-17. 2007..After testing the assay using 2 established blocking antibodies as reference biologicals, the authors performed a proof-of-concept primary screen using a library of 6612 compounds and identified both agonist and antagonist hits... - CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junDFotini Nicolaou
Renal Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
Blood 101:4033-41. 2003..Together, these data indicate that the abnormal expression of the CD11c gene characteristic of HCL is dependent upon activation of the proto-oncogenes ras and junD... - Interaction of purified human proteinase 3 (PR3) with reconstituted lipid bilayersW H Goldmann
Leukocyte Biology and Inflammation Program, Rental Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Eur J Biochem 261:155-62. 1999..The lipid-associated PR3 exhibited two-fold lower Vmax and Km values, and its enzyme activity was slightly more inhibited (Ki) by the natural alpha1-proteinase inhibitor (alpha1-PI) or an autoantibody to PR3... - Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinaseJ L Niles
Department of Medicine, Massachusetts General Hospital, Charlestown 02129
Blood 74:1888-93. 1989..We conclude that the neutrophil antigen responsible for the cytoplasmic staining pattern produced by autoantibodies in patients with active Wegener's granulomatosis is a distinctive serine proteinase... - Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a geneC S Shelley
Department of Medicine, Harvard Medical School, Charlestown, MA 02129
Proc Natl Acad Sci U S A 90:5364-8. 1993..Since MS-2 interacts with a number of different gene promoters and is developmentally regulated in myeloid cells, it may play a major role in regulating myeloid gene expression... - Genetic cause of leukocyte adhesion molecule deficiency. Abnormal splicing and a missense mutation in a conserved region of CD18 impair cell surface expression of beta 2 integrinsC Nelson
Leukocyte Biology and Inflammation Program, Massachusetts General Hospital, Boston
J Biol Chem 267:3351-7. 1992..Both the insertion and the N351----S mutations occurred in a 250 amino acid extracellular region of CD18 that is highly conserved among beta integrins supporting a role for this region in heterodimer formation... - Purification, analysis, and crystal structure of integrinsJian Ping Xiong
Structural Biology Program, Leukocyte Biology and Inflammation Program, Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Charlestown, USA
Methods Enzymol 426:307-36. 2007..In this chapter, we review the methods used to purify and characterize these proteins biophysically and functionally, and to derive their three-dimensional structures... - The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cellsXiangen Li
Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
Development 133:3641-50. 2006..These findings establish a unique regulatory role for ZBP-89, positioned at the interface between early blood and blood vessel development... - Molecular cloning of a novel human hsp70 from a B cell line and its assignment to chromosome 5D M Fathallah
Department of Medicine, Massachusetts General Hospital, Charlestown 02129
J Immunol 151:810-3. 1993..Northern blotting revealed a single mRNA species of 3.0 kb in total RNA prepared from the patient's EBV cell line. In situ hybridization localized the single copy hsp70 RY gene to the long arm of chromosome 5 at 5 q31.1-5 q31.2... - Use of a bovine model to study the role of adhesion molecule CD11/CD18 in hemodialysis-induced neutropeniaHamid Rabb
Nephrology Division, Johns Hopkins University Hospital, Baltimore, MD, USA
Am J Kidney Dis 39:587-93. 2002..These data, although obtained in a small sample, show that a bovine model can be used to study the early neutropenia of dialysis. These data also suggest that a direct role of beta2 integrins may be occurring in this process... - Binding Affinity of Metal Ions to the CD11b A-domain Is Regulated by Integrin Activation and LigandsKaouther Ajroud
Leukocyte Biology and Inflammation Program, Renal Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Biol Chem 279:25483-8. 2004..These findings, which we expect will be applicable in vivo, elucidate a new level of regulation of the integrin-metal-ligand ternary complex and help explain some of the discrepant effects of Ca(2+) on integrin-ligand interactions... - Polycystin-1 activates and stabilizes the polycystin-2 channelG Mark Xu
Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachussetts 02129, USA
J Biol Chem 278:1457-62. 2003..The modulation of polycystin-2 channel activity by polycystin-1 may be important for the various biological processes mediated by this molecular complex... - Does the integrin alphaA domain act as a ligand for its betaA domain?Jose Luis Alonso
Curr Biol 12:R340-2. 2002 - Three-dimensional EM structure of the ectodomain of integrin {alpha}V{beta}3 in a complex with fibronectinBrian D Adair
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
J Cell Biol 168:1109-18. 2005..We conclude that the ectodomain of alphaVbeta3 manifests a bent conformation that is capable of stably binding a physiological ligand in solution... - The structural basis of elasticity in fibrillin-based microfibrilsM Amin Arnaout
Structure 12:734-6. 2004 - Divalent cations and the relationship between alphaA and betaA domains in integrinsKah-Tong Seow
Department of Bio- and Chemoinformatics, Merck KGaA, Frankfurterstr. 250, Darmstadt, Germany
Biochem Pharmacol 64:805-12. 2002..Since the position of these loops are evolutionary conserved but their primary sequence varies between the various betaA domains, they represents potential targets for dissecting functional diversity among integrins...
Research Grants
- TRAINING CELL STRUCTURE AND FUNCTION IN NEPHROLOGYM Amin Arnaout; Fiscal Year: 2007..In addition, trainees can also access laboratories elsewhere at Harvard and MIT. Didactic formal courses are offered at MGH as well as at Harvard Medical School, Harvard School of Public Health, Harvard University and MIT. ..
- Molecular Basis of MO1/LFA-1 DeficiencyM Amin Arnaout; Fiscal Year: 2007..Consequently, four aims are proposed that build on these observations using biochemical, biophysical, crystallographic and genetic approaches in addition to murine models of renal inflammation. ..
- Pathogenesis of ADPKD-role of the transcriptional modulator TAZM Amin Arnaout; Fiscal Year: 2007..The results from these studies will help define a novel pathway regulating the expression level of PKD1 and hence contributing to the renal and extrarenal manifestations of ADPKD. ..
- THE PHAGOCYTE MEMBRANEM Amin Arnaout; Fiscal Year: 2009..3) Identify novel intermediates that regulate inside-out activation of integrins using genetic (RNAi), immunochemical and biochemical approaches. ..
- Pathogenesis of ADPKD-role of the transcriptional modulator TAZM Amin Arnaout; Fiscal Year: 2009..The results from these studies will help define a novel pathway regulating the expression level of PKDl and hence contributing to the renal and extrarenal manifestationsofADPKD. ..
- Molecular Basis of MO1/LFA-1 DeficiencyM Amin Arnaout; Fiscal Year: 2009..Consequently, four aims are proposed that build on these observations using biochemical, biophysical, crystallographic and genetic approaches in addition to murine models of renal inflammation. ..
- Role of the zinc finger transcription factor ZBP89 in blood & vascular developmenM Amin Arnaout; Fiscal Year: 2010..We are proposing a series of studies to pinpoint the role of this factor, and define the developmental networks it coordinates. ..
- Structure and function of integrins in the kidneyM Amin Arnaout; Fiscal Year: 2010..Elucidating how integrins are regulated at an atomic level is essential in understanding their biologic role, information that could be harnessed in devising new therapeutics. ..
- Structure-function of the Proangiogenic Integrin alphaVbM Amin Arnaout; Fiscal Year: 2006....
- MOLECULAR BASIS OF MO1/LFA-L DEFICIENCYM Amin Arnaout; Fiscal Year: 2001..Given the potential role of CD11b/CD18 in inflammation and injury, derivation of specific antagonists of this receptor could have therapeutic benefits. ..
- Structure and Function of beta2 IntegrinM Amin Arnaout; Fiscal Year: 2005..It should also facilitate rational drug design for this class of therapeutic targets. ..
- Metabolomic Analysis of Type 1 Diabetic NephropathyM Amin Arnaout; Fiscal Year: 2005..In this manner, we hone to identify potential metabolomic biomarkers worthy of subsequent validation. ..
- Pathogenesis of ADPKD-role of the transcriptional modulator TAZM Amin Arnaout; Fiscal Year: 2010..The results from these studies will help define a novel pathway regulating the expression level of PKDl and hence contributing to the renal and extrarenal manifestationsofADPKD. ..