1SYS

Crystal structure of HLA, B*4403, and peptide EEPTVIKKY

Summary for 1SYS

• Entry DOI: 10.2210/pdb1sys/pdb
• Descriptor: leukocyte antigen (HLA) class I molecule, Beta-2-microglobulin, Sorting nexin 5, ... (4 entities in total)
• Functional Keywords: hla, mhc, class i, b44, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30481; Secreted: P61769; Early endosome membrane; Peripheral membrane protein; Cytoplasmic side: Q9Y5X3
• Total number of polymer chains: 3
• Total formula weight: 44965.97

Authors

Zernich, D.,Purcell, A.W.,Macdonald, W.A.,Kjer-Nielsen, L.,Ely, L.K.,Laham, N.,Crockford, T.,Mifsud, N.A.,Tait, B.D.,Holdsworth, R.,Brooks, A.G.,Bottomley, S.P.,Beddoe, T.,Peh, C.A.,Rossjohn, J.,McCluskey, J. (deposition date: 2004-04-01, release date: 2004-10-19, Last modification date: 2011-07-13)

Primary citation

Zernich, D.,Purcell, A.W.,Macdonald, W.A.,Kjer-Nielsen, L.,Ely, L.K.,Laham, N.,Crockford, T.,Mifsud, N.A.,Bharadwaj, M.,Chang, L.,Tait, B.D.,Holdsworth, R.,Brooks, A.G.,Bottomley, S.P.,Beddoe, T.,Peh, C.A.,Rossjohn, J.,McCluskey, J.
Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion
J.Exp.Med., 200:13-24, 2004

PubMed Abstract: HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.

PubMed: 15226359
DOI: 10.1084/jem.20031680

Experimental method

X-RAY DIFFRACTION (2.4 Å)