Properties of some variants of human beta2-microglobulin and amyloidogenesis.

The solution structure of human beta2-microglobulin (beta2-m), the
nonpolymorphic component of class I major histocompatibility complex (MHC-I),
was determined by (1)H NMR spectroscopy and restrained modeling calculations.
Compared to previous structural data obtained from the NMR secondary structure
of the isolated protein and the crystal structure of MHC-I, in which the
protein is associated to the heavy-chain component, several differences are
observed. The most important rearrangements were observed for (1) strands V and
VI (loss of the C-terminal and N-terminal end, respectively), (2) interstrand
loop V-VI, and (3) strand I, including the N-terminal segment (displacement
outward of the molecular core). These modifications can be considered as the
prodromes of the amyloid transition. Solvation of the protected regions in
MHC-I decreases the tertiary packing by breaking the contiguity of the surface
hydrophobic patches at the interface with heavy chain and the nearby region at
the surface charge cluster of the C-terminal segment. As a result, the molecule
is placed in a state in which even minor charge and solvation changes in
response to pH or ionic-strength variations can easily compromise the
hydrophobic/hydrophilic balance and trigger the transition into a partially
unfolded intermediate that starts with unpairing of strand I and leads to
polymerization and precipitation into fibrils or amorphous aggregates. The same
mechanism accounts for the partial unfolding and fiber formation subsequent to
Cu(2+) binding, which is shown to occur primarily at His 31 and involve
partially also His 13, the next available His residue along the partial
unfolding pathway.

Verdone G, Corazza A, Viglino P, Pettirossi F, Giorgetti S, Mangione P, Andreola A,
Stoppini M, Bellotti V, Esposito G.
Protein Sci 2002 11(3):487-99
The solution structure of human beta2-microglobulin reveals the prodromes of its amyloid
transition.

Protein science : a publication of the Protein Society
The solution structure of human beta2-microglobulin reveals the prodromes of its amyloid transition.

The solution structure and stability of N-terminally truncated
beta2-microglobulin (deltaN6beta2-m), the major modification in ex vivo
fibrils, have been investigated by a variety of biophysical techniques. The
results show that deltaN6beta2-m has a free energy of stabilization that is
reduced by 2.5 kcal/mol compared to the intact protein. Hydrogen exchange of a
mixture of the truncated and full-length proteins at microM concentrations at
pH 6.5 monitored by electrospray mass spectrometry reveals that deltaN6beta2-m
is significantly less protected than its wild-type counterpart. Analysis of
deltaN6beta2-m by NMR shows that this loss of protection occurs in beta strands
I, III, and part of II. At mM concentration gel filtration analysis shows that
deltaN6beta2-m forms a series of oligomers, including trimers and tetramers,
and NMR analysis indicates that strand V is involved in intermolecular
interactions that stabilize this association. The truncated species of
beta2-microglobulin was found to have a higher tendency to self-associate than
the intact molecule, and unlike wild-type protein, is able to form amyloid
fibrils at physiological pH. Limited proteolysis experiments and analysis by
mass spectrometry support the conformational modifications identified by NMR
and suggest that deltaN6beta2-m could be a key intermediate of a proteolytic
pathway of beta2-microglobulin. Overall, the data suggest that removal of the
six residues from the N-terminus of beta2-microglobulin has a major effect on
the stability of the overall fold. Part of the tertiary structure is preserved
substantially by the disulfide bridge between Cys25 and Cys80, but the pairing
between beta-strands far removed from this constrain is greatly perturbed.

Esposito G, Michelutti R, Verdone G, Viglino P, Hernandez H, Robinson CV, Amoresano A,
Dal Piaz F, Monti M, Pucci P, Mangione P, Stoppini M, Merlini G, Ferri G, Bellotti V.
Protein Sci 2000 9(5):831-45
Removal of the N-terminal hexapeptide from human beta2-microglobulin facilitates protein
aggregation and fibril formation.

Removal of the N-terminal hexapeptide from human beta2-microglobulin facilitates protein aggregation and fibril formation.

Mhc Class I Molecule B5301 Complexed With Peptide Tpydinqml From Gag Protein Of Hiv2

Mhc Class I Molecule B3501 Complexed With Peptide Vplrpmty From The Nef Protein (75-82) Of Hiv1

Mhc Class I Molecule B5301 Complexed With Peptide Ls6 (Kpivqydnf) From The Malaria Parasite P. Falciparum

Decamer-Like Conformation Of A Nano-Peptide Bound To Hla- B3501 Due To Nonstandard Positioning Of The C-Terminus

Antagonist Hiv-1 Gag Peptides Induce Structural Changes In Hla B8-Hiv-1 Gag Peptide (Ggrkkykl-3r Mutation)

Antagonist Hiv-1 Gag Peptides Induce Structural Changes In Hla B8-Hiv-1 Gag Peptide (Ggkkkyql-7q Mutation)

Antagonist Hiv-1 Gag Peptides Induce Structural Changes In Hla B8-Hiv-1 Gag Peptide (Ggkkkykl-Index Peptide)

Antagonist Hiv-1 Gag Peptides Induce Structural Changes In Hla B8-Hiv-1 Gag Peptide (Ggkkkyrl-7r Mutation)

Antagonist Hiv-1 Gag Peptides Induce Structural Changes In Hla B8-Hiv-1 Gag Peptide (Ggkkrykl-5r Mutation)

Complex Of The Human Mhc Class I Glycoprotein Hla-A2 And The T Cell Coreceptor Cd8

Class I Histocompatibility Antigen (Hla-A2.1)BETA 2- MicroglobulinPEPTIDE P1049 COMPLEX

Crystal Structure Of Hla-A0201 Complexed With A Peptide With The Carboxyl-Terminal Group Substituted By A Methyl Group

Complex Between Human T-Cell Receptor B7, Viral Peptide (Tax) And Mhc Class I Molecule Hla-A 0201

Crystal Structure Analysis Of The GammaDELTA T CELL LIGAND T22

Mhc Class I H-2db Complexed With A Sendai Virus Nucleoprotein Peptide

Complex Recognition Of The Supertypic Bw6-Determinant On Hla-B And-C Molecules By The Monoclonal Antibody Sfr8-B6

Hemochromatosis Protein Hfe Complexed With Transferrin Receptor

Crystal Structure Of Hla-A0201OCTAMERIC TAX PEPTIDE Complex

Human Class I Histocompatibility Antigen (Hla-A 0201) In Complex With A Nonameric Peptide From Htlv-1 Tax Protein

Nonstandard Peptide Binding Of Hla-B5101 Complexed With Hiv Immunodominant Epitope Km1(Lppvvakei)

Nonstandard Peptide Binding Of Hla-B5101 Complexed With Hiv Immunodominant Epitope Km2(Taftipsi)

Crystal Structure Determination Of Hla A2 Complexed To Peptide Gp2 With The Substitution (I2lV5LL9V)

Crystal Structure Determination Of Hla-A2.1 Complexed To Gp2 Peptide Variant(I2lV5L)

Structure Of A Complex Between The Human Natural Killer Cell Receptor Kir2dl2 And A Class I Mhc Ligand Hla-Cw3

Crystal Structure Of The Human Mhc-Related Fc Receptor

Cd1b In Complex With Phophatidylinositol

The Antigenic Identity Of Peptide(Slash)mhc Complexes: A Comparison Of The Conformation Of Five Peptides Presented By Hla-A2

Structure Of The Human Class I Histocompatibility Antigen, Hla-A2

The Three-Dimensional Structure Of Hla-B27 At 2.1 Angstroms Resolution Suggests A General Mechanism For Tight Peptide Binding To Mhc

Different Length Peptides Bind To Hla-Aw68 Similarly At Their Ends But Bulge Out In The Middle

Crystal Structure Of Human Class I Mhc (Hla-A2.1) Complexed With Beta 2-Microglobulin And Hiv-Rt Variant Peptide I1y

Crystal Structure Of Hla-A0201MAGE-A4-Peptide Complex

Crystal Structure Of Class I Mhc A2 In Complex With Peptide P1058

Crystal Structure Of Class I Mhc A2 In Complex With Peptide P1049-5v

Crystal Structure Of Class I Mhc A2 In Complex With Peptide P1049-6v

Crystal Structure Of The Human Cytomegalovirus Protein Us2 Bound To The Mhc Class I Molecule Hla-A2TAX

Crystal Structure Of The Human Natural Killer Cell Inhibitory Receptor Kir2dl1 Bound To Its Mhc Ligand Hla-Cw4

Crystal Structure Of Hla-A20201 In Complex With A Decameric Altered Peptide Ligand From The Mart-1MELAN-A

Crystal Structure Of Hla-A20201 In Complex With A Nonameric Altered Peptide Ligand (Algigiltv) From The Mart- 1MELAN-A.

Nmr Solution Structure Of The Human Beta2-Microglobulin

The Human Non-Classical Major Histocompatibility Complex Molecule Hla-E

Crystal Structure Of Monomeric Human Beta-2-Microglobulin

Xenoreactive Complex Ahiii 12.2 Tcr Bound To P1049HLA-A2.1

Hla B8 In Complex With An Epstein Barr Virus Determinant

Crystal Structure Of Hla B4402 In Complex With Hla Dpa0201 Peptide

The Crystal Structure Of Lc13 Tcr In Complex With Hlab8-Ebv Peptide Complex

A Natural Selected Dimorphism In Hla B44 Alters Self, Peptide Reportoire And T Cell Recognition.

Crystal Structure Of Hla-B2709 Complexed With The Vasoactive Intestinal Peptide Type 1 Receptor (Vipr) Peptide (Residues 400-408)

A Structural Basis For Immunodominant Human T-Cell Receptor Recognition.

Crystal Structure Of Hla-B2705 Complexed With The Vasoactive Intestinal Peptide Type 1 Receptor (Vipr) Peptide (Residues 400-408)

Crystal Structure Of Cd1a In Complex With A Sulfatide

Crystal Structure Of Hla-A2 Bound To Lir-1, A Host And Viral Mhc Receptor

Beta2 Microglobulin Mutant H31y Displays Hints For Amyloid Formations

Structures Of Hla-A1101 In Complex With Immunodominant Nonamer And Decamer Hiv-1 Epitopes Clearly Reveal The Presence Of A Middle Anchor Residue

Human Class I Histocompatibility Antigen (Hla-A 0201) Complex With A Nonameric Peptide From Melanoma-Associated Antigen 3 (Residues 271-279)

Mhc Class I H-2db Complexed With Glycopeptide K3g

Poor Binding Of A Her-2NEU EPITOPE (GP2) TO HLA-A2.1 Is Due To A Lack Of Interactions In The Center Of The Peptide

Crystal Structure Of Human A6 Tcr Complexed With Hla-A2 Bound To Altered Htlv-1 Tax Peptide P6a

Structure Of Human A6-Tcr Bound To Hla-A2 Complexed With Altered Htlv-1 Tax Peptide V7r

Structure Of A6-Tcr Bound To Hla-A2 Complexed With Altered Htlv-1 Tax Peptide Y8a

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9-3a

Crystal Structure Analysis Of Ny-Eso-1 Epitope, Sllmwitqc, In Complex With Hla-A2

Crystal Structure Analysis Of Ny-Eso-1 Epitope Analogue, Sllmwitqa, In Complex With Hla-A2

Crystal Structure Analysis Of Ny-Eso-1 Epitope Analogue, Sllmwitqs, In Complex With Hla-A2

Crystal Structure Of Hla, B4403, And Peptide Eeptvikky

Hla-B4405 Complexed To The Dominant Self Ligand Eefgraygf

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9-3f6i8v

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9-4l

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9-5v

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9-6a

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9-6i

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9, Monoclinic Crystal

Structural Basis For Degenerate Recognition Of Hiv Peptide Variants By Cytotoxic Lymphocyte, Variant Sl9, Orthorhombic Crystal

The Htree-Dimensional Structure Of A Class I Major Histocompatibility Complex Molecule Missing The Alpha3 Domain Of The Heavy Chain

Crystal Structure Of Melanoma Antigen Gp100(209-217) Bound To Human Class I Mhc Hla-A2

Crystal Structure Of Modified Melanoma Antigen Gp100(209- T2m) Bound To Human Class I Mhc Hla-A2

The Crystal Structure Of Human Cd1b With A Bound Bacterial Glycolipid

Crystal Structure Of Hla-B2705 Complexed With The Latent Membrane Protein 2 Peptide (Lmp2)of Epstein-Barr Virus

Crystal Structure Of Hla-B2709 Complexed With The Latent Membrane Protein 2 Peptide (Lmp2) Of Epstein-Barr Virus

The Crystal Structure Of Class I Major Histocompatibility Complex, H-2kd At 2.0 A Resolution

Crystal Structure Of Hla-B2705 Complexed With The Self- Peptide Tis From Egf-Response Factor 1

Crystal Structure Of Hla-B2709 Complexed With The Self- Peptide Tis From Egf-Response Factor 1

Crystal Structure Of Hla-A1:mage-A1 In Complex With Fab-Hyb3

Crystal Structure Of Hla-A1101 With Sars Nucleocapsid Peptide

Conformational Restraints And Flexibility Of 14-Meric Peptides In Complex With Hla-B3501

Crystal Structures Of Hla-B1501 In Complex With Peptides From Human Ubch6 And Epstein-Barr Virus Ebna-3

Crystal Structure Of Cd1a In Complex With A Synthetic Mycobactin Lipopeptide

Crystal Structure Of Hla-B3501 Presenting 13-Mer Ebv Antigen Lpeplpqgqltay

Crystal Structure Of Hla-B3508 Presenting 13-Mer Ebv Antigen Lpeplpqgqltay

Crystal Structure Of The Murine Mhc Class Ib Molecule M10.5

Crystal Structure Of Hla-B3501 Presenting An 11-Mer Ebv Antigen Eplpqgqltay

The Crystal Structure Of Human Cd1d With And Without Alpha- Galactosylceramide

Crystal Structure Of The First Class Mhc Mamu And Tat-Tl8 Complex

Crystal Structure Of Hla-B2705 Complexed With The Glucagon Receptor (Gr) Peptide (Residues 412-420)

Crystal Structure Of Sb27 Tcr In Complex With Hla-B3508- 13mer Peptide

Crystal Structure Of Htlv-1 Tax Peptide Bound To Human Class I Mhc Hla-A2 With The E63q And K66a Mutations In The Heavy Chain.

Crystal Structure Of Htlv-1 Tax Peptide Bound To Human Class I Mhc Hla-A2 With The K66a Mutation In The Heavy Chain.

The Immunogenicity Of A Viral Cytotoxic T Cell Epitope Is Controlled By Its Mhc-Bound Conformation

Crystal Structure Of Hla-A2402 Complexed With A Telomerase Peptide

Structural And Kinetic Basis For Heightened Immunogenicity Of T Cell Vaccines

Crystal Structures And Kir3dl1 Recognition Of Three Immunodominant Viral Peptides Complexed To Hla-B2705

Structures Of Three Hiv-1 Hla-B5703-Peptide Complexes And Identification Of Related Hlas Potentially Associated With Long-Term Non-Progression

Conflicting Selective Forces Affect Cd8 T-Cell Receptor Contact Sites In An Hla-A2 Immunodominant Hiv Epitope.

The Crystal Structure Of H-2db Complexed With A Partial Peptide Epitope Suggests An Mhc Class I Assembly- Intermediate

Insights Into Crossreactivity In Human Allorecognition: The Structure Of Hla-B35011 Presenting An Epitope Derived From Cytochrome P450.

Three Dimensional Structure Of A Peptide Extending Out One End Of A Class I Mhc Binding Site

Crystal Structure Of Disulfide-Linked Hla-G Dimer

The Crystal Structure Of Human Beta2-Microglobulin

Crystal Structure Of Lilrb2(Lir2ILT4CD85D) COMPLEXED WITH Hla-G

Structure Of The Hla-E-VmaprtlilKK50.4 TCR COMPLEX

Directed Evolution Of Human T-Cell Receptor Cdr2 Residues By Phage Display Dramatically Enhances Affinity For Cognate Peptide-Mhc Without Apparent Cross-Reactivity

Murine Mhc Class I H-2db In Complex With Human B2- Microglobulin And Lcmv-Derived Immunodminant Peptide Gp33

A Native To Amyloidogenic Transition Regulated By A Backbone Trigger

The Role Of T Cell Receptor Alpha Genes In Directing Human Mhc Restriction

Human Class I Mhc Hla-A2 In Complex With The Modified Htlv- 1 Tax (Y5k-4-[3-Indolyl]-Butyric Acid) Peptide

The Complex Between Tcr A6 And Human Class I Mhc Hla-A2 With The Modified Htlv-1 Tax (Y5k-4-[3-Indolyl]-Butyric Acid) Peptide

Human Class I Mhc Hla-A2 In Complex With The Decameric Melan-AMART-1(26-35) Peptide

Human Class I Mhc Hla-A2 In Complex With The Nonameric Melan-AMART-1(27-35) Peptide Having A27l Substitution

Human Class I Mhc Hla-A2 In Complex With The Nonameric Melan-AMART-1(27-35) Peptide Having A28l Substitution

Human Class I Mhc Hla-A2 In Complex With The Native Nonameric Melan-AMART-1(27-35) Peptide

Human Cd1b In Complex With Endogenous Phosphatidylcholine And Spacer

Crystal Structure Of Hla-B3501 Presenting The Human Cytochrome P450 Derived Peptide, Kpivvlhgy

Crystal Structure Of Hla-B5703 And Hiv-1 Peptide

Specificity Pockets For The Side Chains Of Peptide Antigens In Hla-Aw68

Hla-A1101 In Complex With Hbv Peptide Homologue

Large Cdr3a Loop Alteration As A Function Of Mhc Mutation.

Crystal Structure Of Hla-B3508 Presenting Ebv Peptide Eplpqgqltay At 1.7a

Crystal Structure Of Els4 Tcr Bound To Hla-B3508 Presenting Ebv Peptide Eplpqgqltay At 1.7a

Crystal Structures Of High Affinity Human T-Cell Receptors Bound To Pmhc Reveal Native Diagonal Binding Geometry

Crystal Structure Of Cd1d-Lipid-Antigen Complexed With Beta- 2-Microglobulin, Nkt15 Alpha-Chain And Nkt15 Beta-Chain

Crystal Structures Of High Affinity Human T-Cell Receptors Bound To Pmhc Revealnative Diagonal Binding Geometry Tcr Clone C5c1 Complexed With Mhc

Crystal Structure Of Hla-B5701, Presenting The Self Peptide, Lsspvtksf

T Cell Cross-Reactivity And Conformational Changes During Tcr Engagement

Solution Structure Of W60g Mutant Of Human Beta2- Microglobulin

The Structural Dynamics And Energetics Of An Immunodominant T-Cell Receptor Are Programmed By Its Vbeta Domain

The High Resolution Crystal Structure Of Beta2- Microglobulin Under Physiological Conditions

Crystal Structure Of The Human Beta-2 Microglobulin Mutant W60g

Citrullination-Dependent Differential Presentation Of A Self-Peptide By Hla-B27 Subtypes

Crystal Structure Of Hla-B2705 Complexed With The Citrullinated Vasoactive Intestinal Peptide Type 1 Receptor (Vipr) Peptide (Residues 400-408)

Crystal Structure Of Hla B3508 In Complex With A Hcmv 12- Mer Peptide From The Pp65 Protein

Crystal Structure Of Hla B3508 In Complex With A Hcmv 8- Mer Peptide From The Pp65 Protein

Crystal Structure Of A Sars Corona Virus Derived Peptide Bound To The Human Major Histocompatibility Complex Class I Molecule Hla-B1501

Structure Of Ul18, A Peptide-Binding Viral Mhc Mimic, Bound To A Host Inhibitory Receptor

pI 5.3 beta 2-microglobulin, BM [human, urine, chronic renal failure patient, Peptide, 98 aa]

beta-2-microglobulin precursor [Homo sapiens]

Beta-2-microglobulin precursor [Contains: Beta-2-microglobulin form pI 5.3]

1H chemical shift assignments for a mutant of human beta2-microglobulin where
ARG 3 is replaced by Ala

beta2-microglobulin with the first 3 residues

DN3 beta2-microglobulin without the first 3 residues

DN3 beta2-microglobulin (H31Y mutant and with the first 3 residues)