Class I MHC is stabilized against thermal denaturation by physiological concentrations of NaCl.


Abstract

Class I MHC molecules are ternary complexes composed of an allotype specific heavy chain, a noncovalently associated protein beta(2)-microglobulin (beta(2)m), and a peptide. The complexes are assembled in the endoplasmic reticulum by a complex series of chaperones and peptide-loading mechanisms. In the absence of beta(2)m or peptide, very little class I heavy chain is transported to the surface of the cell. Complexes that do not contain all three parts of the protein are not made productively in vivo and not at all in vitro. The ability of the complex to withstand thermal denaturation in vitro has been shown to be related to the binding affinity of the peptide. Paradoxically, some low-affinity peptide complexes denature at or below human basal body temperatures in vitro but are effective biological agents in vivo. Here we show that these complexes are stabilized against thermal denaturation by physiological cosolvents and maximally stabilized by 150 mM NaCl. While the degree of stabilization by 150 mM NaCl is greatest for low-affinity peptide/MHC complexes, the mechanism of stabilization is independent of peptide sequence. This effect is hypothesized to occur by multiple mechanisms including increasing the affinity of beta(2)m for the complex and charge screening. Study holds ProTherm entries: 8533, 8534, 8535, 8536, 8537, 8538, 8539, 8540, 8541, 8542, 8543, 8544, 8545, 8546, 8547, 8548, 8549, 8550, 8551, 8552, 8553, 8554, 8555, 8556, 8557, 8558 Extra Details: The peptide is IISAVVGIL chaperones; peptide-loading mechanisms; binding affinity;,peptide; charge screening

Submission Details

ID: BW9QVoo7

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:36 p.m.

Version: 1

Publication Details
Batalia MA;Kirksey TJ;Sharma A;Jiang L;Abastado JP;Yan S;Zhao R;Collins EJ,Biochemistry (2000) Class I MHC is stabilized against thermal denaturation by physiological concentrations of NaCl. PMID:10913316
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1B3J 1998-12-11T00:00:00+0000 3.0 STRUCTURE OF THE MHC CLASS I HOMOLOG MIC-A, A GAMMADELTA T CELL LIGAND
1HYR 2001-01-21T00:00:00+0000 2.7 CRYSTAL STRUCTURE OF HUMAN MICA IN COMPLEX WITH NATURAL KILLER CELL RECEPTOR NKG2D
1INQ 2001-05-14T00:00:00+0000 2.2 Structure of Minor Histocompatibility Antigen peptide, H13a, complexed to H2-Db
1JUF 2001-08-24T00:00:00+0000 2.0 Structure of Minor Histocompatibility Antigen peptide, H13b, complexed to H2-Db
1LD9 1997-04-24T00:00:00+0000 2.4 THE THREE-DIMENSIONAL STRUCTURE OF AN H-2LD PEPTIDE COMPLEX EXPLAINS THE UNIQUE INTERACTION OF LD WITH BETA2M AND PEPTIDE
1LDP 1998-03-15T00:00:00+0000 3.1 CRYSTAL STRUCTURE OF MURINE MHC CLASS I H-2LD WITH A MIXTURE OF BOUND PEPTIDES
2E7L 2007-01-11T00:00:00+0000 2.5 Structure of a high-affinity mutant of the 2C TCR in complex with Ld/QL9
2OI9 2007-01-10T00:00:00+0000 2.35 Structure of the 2C/Ld/QL9 allogeneic complex
3E2H 2008-08-05T00:00:00+0000 3.8 Structure of the m67 high-affinity mutant of the 2C TCR in complex with Ld/QL9
3E3Q 2008-08-07T00:00:00+0000 2.95 Structure of the 3alpham13 high-affinity mutant of the 2C TCR in complex with Ld/QL9

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
99.0 B H-2 class I histocompatibility antigen, D-B alpha chain P01887 B2MG_MOUSE
95.4 A H-2 class I histocompatibility antigen, D-B alpha chain P01896 HA1Z_MOUSE
93.8 A H-2 class I histocompatibility antigen, D-B alpha chain P01897 HA1L_MOUSE
100.0 A H-2 class I histocompatibility antigen, D-B alpha chain P01899 HA11_MOUSE
95.8 Minor histocompatibility antigen H13 Q8TCT9 HM13_HUMAN
100.0 Minor histocompatibility antigen H13 Q9D8V0 HM13_MOUSE
100.0 MHC class I polypeptide-related sequence A Q29983 MICA_HUMAN