3qda

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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== Publication Abstract from PubMed ==
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ABSTRACT: BACKGROUND: We have recently discovered that the two tryptophans of human beta2-microglobulin have distinctive roles within the structure and function of the protein. Deeply buried in the core, Trp95 is essential for folding stability, whereas Trp60, which is solvent-exposed, plays a crucial role in promoting the binding of beta2-microglobulin to the heavy chain of the class I major histocompatibility complex (MHCI). We have previously shown that the thermodynamic disadvantage of having Trp60 exposed on the surface is counter-balanced by the perfect fit between it and a cavity within the MHCI heavy chain that contributes significantly to the functional stabilization of the MHCI. Therefore, based on the peculiar differences of the two tryptophans, we have analysed the evolution of beta2-microglobulin with respect to these residues. RESULTS: Having defined the beta2-microglobulin protein family, we performed multiple sequence alignments and analysed the residue conservation in homologous proteins to generate a phylogenetic tree. Our results indicate that Trp60 is highly conserved, whereas some species have a Leu in position 95; the replacement of Trp95 with Leu destabilizes beta2-microglobulin by 1 kcal/mol and accelerates the kinetics of unfolding. Both thermodynamic and kinetic data fit with the crystallographic structure of the Trp95Leu variant, which shows how the hydrophobic cavity of the wild-type protein is completely occupied by Trp95, but is only half filled by Leu95. CONCLUSIONS: We have established that the functional Trp60 has been present within the sequence of beta2-microglobulin since the evolutionary appearance of proteins responsible for acquired immunity, whereas the structural Trp95 was selected and stabilized, most likely, for its capacity to fully occupy an internal cavity of the protein thereby creating a better stabilization of its folded state.
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The two tryptophans of beta2-microglobulin have distinct roles in function and folding and might represent two independent responses to evolutionary pressure.,Raimondi S, Barbarini N, Mangione P, Esposito G, Ricagno S, Bolognesi M, Zorzoli I, Marchese L, Soria C, Bellazzi R, Monti M, Stoppini M, Stefanelli M, Magni P, Bellotti V BMC Evol Biol. 2011 Jun 10;11:159. PMID:21663612<ref>PMID:21663612</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
==See Also==

Current revision

Crystal structure of W95L beta-2 microglobulin

PDB ID 3qda

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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