NMR structure of a fungal virulence factor reveals structural homology with mammalian saposin B

被引：25

作者：

Beck, Moriah R. ^{[1
,2
,3
]}

DeKoster, Gregory T. ^{[2
]}

Cistola, David P. ^{[2
]}

Goldman, William E. ^{[1
,4
]}

机构：

[1] Washington Univ, Dept Mol Microbiol, St Louis, MO 63110 USA

[2] Washington Univ, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA

[3] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

来源：

MOLECULAR MICROBIOLOGY | 2009年 / 72卷 / 02期

基金：

美国国家卫生研究院;

关键词：

SPHINGOLIPID ACTIVATOR PROTEINS; AMBIGUOUS DISTANCE RESTRAINTS; HISTOPLASMA-CAPSULATUM; NK-LYSIN; CRYSTAL-STRUCTURE; INTRACELLULAR PARASITISM; MEMBRANE INTERACTIONS; AUTOMATED ASSIGNMENT; CALCIUM-DEPENDENCE; BACTERIOCIN AS-48;

D O I：

10.1111/j.1365-2958.2009.06647.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The fungal protein CBP (calcium binding protein) is a known virulence factor with an unknown virulence mechanism. The protein was identified based on its ability to bind calcium and its prevalence as Histoplasma capsulatum's most abundant secreted protein. However, CBP has no sequence homology with other CBPs and contains no known calcium binding motifs. Here, the NMR structure of CBP reveals a highly intertwined homodimer and represents the first atomic level NMR model of any fungal virulence factor. Each CBP monomer is comprised of four alpha-helices that adopt the saposin fold, characteristic of a protein family that binds to membranes and lipids. This structural homology suggests that CBP functions as a lipid binding protein, potentially interacting with host glycolipids in the phagolysosome of host cells.

引用

页码：344 / 353

页数：10

共 52 条

[1] Crystal structure of saposin B reveals a dimeric shell for lipid binding [J].

Ahn, VE ;

Faull, KF ;

Whitelegge, JP ;

Fluharty, AL ;

Privé, GG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (01) :38-43

[2] Crystal structures of saposins A and C [J].

Ahn, Victoria E. ;

Leyko, Paul ;

Alattia, Jean-Rene ;

Chen, Lu ;

Prive, Gilbert G. .

PROTEIN SCIENCE, 2006, 15 (08) :1849-1857

[3] Direct visualization of saposin remodelling of lipid bilayers [J].

Alattia, Jean-Rene ;

Shaw, James E. ;

Yip, Christopher M. ;

Prive, Gilbert G. .

JOURNAL OF MOLECULAR BIOLOGY, 2006, 362 (05) :943-953

[4] Granulysin crystal structure and a structure-derived lytic mechanism [J].

Anderson, DH ;

Sawaya, MR ;

Cascio, D ;

Ernst, W ;

Modlin, R ;

Krensky, A ;

Eisenberg, D .

JOURNAL OF MOLECULAR BIOLOGY, 2003, 325 (02) :355-365

[5] Calcium dependence and binding in cultures of Histoplasma capsulatum [J].

Batanghari, JW ;

Goldman, WE .

INFECTION AND IMMUNITY, 1997, 65 (12) :5257-5261

[6]

Batanghari JW, 1998, MOL MICROBIOL, V27, P531, DOI 10.1046/j.1365-2958.1998.00697.x

[7] Structural features responsible for the biological stability of Histoplasma's virulence factor CBP [J].

Beck, Moriah R. ;

DeKoster, Gregory T. ;

Hambly, David M. ;

Gross, Michael L. ;

Cistola, David P. ;

Goldman, William E. .

BIOCHEMISTRY, 2008, 47 (15) :4427-4438

[8] A short guided tour through functional and structural features of saposin-like proteins [J].

Bruhn, H .

BIOCHEMICAL JOURNAL, 2005, 389 :249-257

[9] Comparative modeling of amoebapores and granulysin based on the NK-lysin structure - Structure and functional implications [J].

Bruhn, H ;

Leippe, M .

BIOLOGICAL CHEMISTRY, 1999, 380 (7-8) :1001-1007

[10] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

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