2vb5
From Proteopedia
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| - | + | {{STRUCTURE_2vb5| PDB=2vb5 | SCENE= }} | |
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'''SOLUTION STRUCTURE OF W60G MUTANT OF HUMAN BETA2-MICROGLOBULIN''' | '''SOLUTION STRUCTURE OF W60G MUTANT OF HUMAN BETA2-MICROGLOBULIN''' | ||
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| + | ==Overview== | ||
| + | Amyloidosis associated to hemodialysis is caused by persistently high beta(2)-microglobulin (beta(2)m) serum levels. beta(2)m is an intrinsically amyloidogenic protein whose capacity to assemble into amyloid fibrils in vitro and in vivo is concentration dependent; no beta(2)m genetic variant is known in the human population. We investigated the roles of two evolutionary conserved Trp residues in relation to beta(2)m structure, function and folding/misfolding by means of a combined biophysical and functional approach. We show that Trp60 plays a functional role in promoting the association of beta(2)m in class I major histocompatibility complex; it is exposed to the solvent at the apex of a protein loop in order to accomplish such function. The Trp60-->Gly mutation has a threefold effect: it stabilizes beta(2)m, inhibits beta(2)m amyloidogenic propensity and weakens the interaction with the class I major histocompatibility complex heavy chain. On the contrary, Trp95 is buried in the beta(2)m core; the Trp95-->Gly mutation destabilizes the protein, which is unfolded in solution, yielding nonfibrillar beta(2)m aggregates. Trp60 and Trp95 therefore play differential and complementary roles in beta(2)m, being relevant for function (Trp60) and for maintenance of a properly folded structure (Trp95) while affecting in distinct ways the intrinsic propensity of wild-type beta(2)m towards self-aggregation into amyloid fibrils. | ||
==About this Structure== | ==About this Structure== | ||
2VB5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VB5 OCA]. | 2VB5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VB5 OCA]. | ||
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| + | ==Reference== | ||
| + | The controlling roles of Trp60 and Trp95 in beta2-microglobulin function, folding and amyloid aggregation properties., Esposito G, Ricagno S, Corazza A, Rennella E, Gumral D, Mimmi MC, Betto E, Pucillo CE, Fogolari F, Viglino P, Raimondi S, Giorgetti S, Bolognesi B, Merlini G, Stoppini M, Bolognesi M, Bellotti V, J Mol Biol. 2008 May 9;378(4):885-95. Epub 2008 Mar 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18395224 18395224] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Stoppini, M.]] | [[Category: Stoppini, M.]] | ||
[[Category: Viglino, P.]] | [[Category: Viglino, P.]] | ||
| - | [[Category: | + | [[Category: Amyloid disease]] |
| - | [[Category: | + | [[Category: Glycation]] |
| - | [[Category: | + | [[Category: Glycoprotein]] |
| - | [[Category: | + | [[Category: Immune response]] |
| - | [[Category: | + | [[Category: Immune system]] |
| - | [[Category: | + | [[Category: Immunoglobulin constant domain]] |
| - | [[Category: | + | [[Category: Immunoglobulin domain]] |
| - | [[Category: | + | [[Category: Mhc i]] |
| - | [[Category: | + | [[Category: Secreted]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:34:07 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:34, 30 April 2008
SOLUTION STRUCTURE OF W60G MUTANT OF HUMAN BETA2-MICROGLOBULIN
Overview
Amyloidosis associated to hemodialysis is caused by persistently high beta(2)-microglobulin (beta(2)m) serum levels. beta(2)m is an intrinsically amyloidogenic protein whose capacity to assemble into amyloid fibrils in vitro and in vivo is concentration dependent; no beta(2)m genetic variant is known in the human population. We investigated the roles of two evolutionary conserved Trp residues in relation to beta(2)m structure, function and folding/misfolding by means of a combined biophysical and functional approach. We show that Trp60 plays a functional role in promoting the association of beta(2)m in class I major histocompatibility complex; it is exposed to the solvent at the apex of a protein loop in order to accomplish such function. The Trp60-->Gly mutation has a threefold effect: it stabilizes beta(2)m, inhibits beta(2)m amyloidogenic propensity and weakens the interaction with the class I major histocompatibility complex heavy chain. On the contrary, Trp95 is buried in the beta(2)m core; the Trp95-->Gly mutation destabilizes the protein, which is unfolded in solution, yielding nonfibrillar beta(2)m aggregates. Trp60 and Trp95 therefore play differential and complementary roles in beta(2)m, being relevant for function (Trp60) and for maintenance of a properly folded structure (Trp95) while affecting in distinct ways the intrinsic propensity of wild-type beta(2)m towards self-aggregation into amyloid fibrils.
About this Structure
2VB5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The controlling roles of Trp60 and Trp95 in beta2-microglobulin function, folding and amyloid aggregation properties., Esposito G, Ricagno S, Corazza A, Rennella E, Gumral D, Mimmi MC, Betto E, Pucillo CE, Fogolari F, Viglino P, Raimondi S, Giorgetti S, Bolognesi B, Merlini G, Stoppini M, Bolognesi M, Bellotti V, J Mol Biol. 2008 May 9;378(4):885-95. Epub 2008 Mar 8. PMID:18395224 Page seeded by OCA on Wed Apr 30 13:34:07 2008
Categories: Homo sapiens | Single protein | Bellotti, V. | Bolognesi, B. | Corazza, A. | Esposito, G. | Fogolari, F. | Giorgetti, S. | Gumral, D. | Merlini, G. | Mimmi, M C. | Raimondi, S. | Rennella, E. | Stoppini, M. | Viglino, P. | Amyloid disease | Glycation | Glycoprotein | Immune response | Immune system | Immunoglobulin constant domain | Immunoglobulin domain | Mhc i | Secreted
