5u52

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2 helix minimized version of the B-domain from Protein A (Z34C0 bound to IgG1 Fc (monoclinic form)

Structural highlights

5u52 is a 4 chain structure with sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.942Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IGHG1_HUMAN Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:254500. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.

Function

IGHG1_HUMAN

Publication Abstract from PubMed

The well-studied B-domain from Staphylococcal protein A is a 59 amino acid three-helix bundle that binds the Fc portion of IgG with a dissociation constant of ~35 nM. The B-domain variant bearing a Gly to Ala mutation (=Z-domain) has been the subject of efforts to minimize a domain's size while retaining its function. We report X-ray crystallographic characterization of three steps in such a process using complexes with Fc: the full three-helix Z-domain, a 34 amino acid two-helix version called Z34C and a 13 amino acid single helix stabilized with an exo-helix tether, called LH1.

3-2-1: Structural insights from stepwise shrinkage of a three-helix Fc-binding domain to a single helix.,Ultsch M, Braisted A, Maun HR, Eigenbrot C Protein Eng Des Sel. 2017 May 5:1-7. doi: 10.1093/protein/gzx029. PMID:28475752^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ultsch M, Braisted A, Maun HR, Eigenbrot C. 3-2-1: Structural insights from stepwise shrinkage of a three-helix Fc-binding domain to a single helix. Protein Eng Des Sel. 2017 May 5:1-7. doi: 10.1093/protein/gzx029. PMID:28475752 doi:http://dx.doi.org/10.1093/protein/gzx029