3wkn
From Proteopedia
Crystal structure of the artificial protein AFFinger p17 (AF.p17) complexed with Fc fragment of human IgG
Structural highlights
DiseaseIGHG1_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. FunctionPublication Abstract from PubMedProtein engineering that exploits known functional peptides holds great promise for generating novel functional proteins. Here we propose a combinatorial approach, termed adaptive assembly, which provides a tailor-made protein scaffold for a given functional peptide. A combinatorial library was designed to create a tailor-made scaffold, which was generated from beta hairpins derived from a 10-residue minimal protein "chignolin" and randomized amino acid sequences. We applied adaptive assembly to a peptide with low affinity for the Fc region of human immunoglobulin G, generating a 54-residue protein AF.p17 with a 40,600-fold enhanced affinity. The crystal structure of AF.p17 complexed with the Fc region revealed that the scaffold fixed the active conformation with a unique structure composed of a short alpha helix, beta hairpins, and a loop-like structure. Adaptive assembly can take full advantage of known peptides as assets for generating novel functional proteins. Adaptive Assembly: Maximizing the Potential of a Given Functional Peptide with a Tailor-Made Protein Scaffold.,Watanabe H, Honda S Chem Biol. 2015 Aug 18. pii: S1074-5521(15)00289-6. doi:, 10.1016/j.chembiol.2015.07.015. PMID:26299673[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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