2VB5

Solution structure of W60G mutant of human beta2-microglobulin

Summary for 2VB5

• Entry DOI: 10.2210/pdb2vb5/pdb
• Related: 1A1M 1A1N 1A1O 1A6Z 1A9B 1A9E 1AGB 1AGC 1AGD 1AGE 1AGF 1AKJ 1AO7 1B0G 1B0R 1BD2 1BMG 1C16 1CE6 1CG9 1DE4 1DUY 1DUZ 1E27 1E28 1EEY 1EEZ 1EFX 1EXU 1GZP 1GZQ 1HHG 1HHH 1HHI 1HHJ 1HHK 1HLA 1HSA 1HSB 1I1F 1I1Y 1I4F 1I7R 1I7T 1I7U 1IM3 1IM9 1JF1 1JGD 1JGE 1JHT 1JNJ 1K5N 1KPR 1KTL 1LDS 1LP9 1M05 1M6O 1MHE 1MI5 1N2R 1OF2 1OGA 1OGT 1ONQ 1P7Q 1PY4 1Q94 1QEW 1QLF 1QQD 1QR1 1QRN 1QSE 1QSF 1QVO 1R3H 1S9W 1S9X 1S9Y 1SYS 1SYV 1TMC 1TVB 1TVH 1UQS 1UR7 1UXS 1UXW 1VGK 1W0V 1W0W 1W72 1X7Q 1XH3 1XR8 1XR9 1XZ0 1YDP 1YPZ 1ZS8 1ZSD 1ZT4 2A83 2AK4 2AV7 2AXF 2AXG 2BCK 2BNQ 2BNR 2BSR 2BSS 2BST 2BSU 2BSV 2BVQ 2C7U 2CII 2CIK 2CLR 2D31 2D4D 2D4F 2E8D 2ESV 2F74 2F8O 2H26 2HJK 2HJL 2HLA 2JCC 2UWE 2V2W 2V2X 3HLA
• NMR Information: BMRB: 15480
• Descriptor: BETA-2-MICROGLOBULIN (1 entity in total)
• Functional Keywords: immunoglobulin constant domain, immune system, amyloid disease, immune response, mhc i, secreted, glycation, glycoprotein, immunoglobulin domain
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 11750.20

Authors

Esposito, G.,Corazza, A.,Rennella, E.,Gumral, D.,Mimmi, M.C.,Fogolari, F.,Viglino, P.,Raimondi, S.,Giorgetti, S.,Bolognesi, B.,Merlini, G.,Stoppini, M.,Bellotti, V. (deposition date: 2007-09-06, release date: 2007-09-25, Last modification date: 2023-06-14)

Primary citation

Esposito, G.,Ricagno, S.,Corazza, A.,Rennella, E.,Gumral, D.,Mimmi, M.C.,Betto, E.,Pucillo, C.E.M.,Fogolari, F.,Viglino, P.,Raimondi, S.,Giorgetti, S.,Bolognesi, B.,Merlini, G.,Stoppini, M.,Bolognesi, M.,Bellotti, V.
The Controlling Roles of Trp60 and Trp95 in Beta2-Microglobulin Function, Folding and Amyloid Aggregation Properties.
J.Mol.Biol., 378:885-, 2008

PubMed Abstract: 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.

PubMed: 18395224
DOI: 10.1016/J.JMB.2008.03.002

Experimental method

SOLUTION NMR