PMID- 19543291
OWN - NLM
STAT- MEDLINE
DCOM- 20090730
LR  - 20211203
IS  - 1545-9985 (Electronic)
IS  - 1545-9993 (Print)
IS  - 1545-9985 (Linking)
VI  - 16
IP  - 7
DP  - 2009 Jul
TI  - Structure of a lamprey variable lymphocyte receptor in complex with a protein 
      antigen.
PG  - 725-30
LID - 10.1038/nsmb.1619 [doi]
AB  - Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins that 
      mediate adaptive immunity in jawless vertebrates. VLRs are fundamentally 
      different from the antibodies of jawed vertebrates, which consist of 
      immunoglobulin (Ig) domains. We determined the structure of an anti-hen egg white 
      lysozyme (HEL) VLR, isolated by yeast display, bound to HEL. The VLR, whose 
      affinity resembles that of IgM antibodies, uses nearly all its concave surface to 
      bind the protein, in addition to a loop that penetrates into the enzyme active 
      site. The VLR-HEL structure combined with sequence analysis revealed an almost 
      perfect match between ligand-contacting positions and positions with highest 
      sequence diversity. Thus, it is likely that we have defined the generalized 
      antigen-binding site of VLRs. We further demonstrated that VLRs can be 
      affinity-matured by 13-fold to affinities as high as those of IgG antibodies, 
      making VLRs potential alternatives to antibodies for biotechnology applications.
FAU - Velikovsky, C Alejandro
AU  - Velikovsky CA
AD  - Center for Advanced Research in Biotechnology, WM Keck Laboratory for Structural 
      Biology, University of Maryland Biotechnology Institute, Rockville, Maryland, 
      USA.
FAU - Deng, Lu
AU  - Deng L
FAU - Tasumi, Satoshi
AU  - Tasumi S
FAU - Iyer, Lakshminarayan M
AU  - Iyer LM
FAU - Kerzic, Melissa C
AU  - Kerzic MC
FAU - Aravind, L
AU  - Aravind L
FAU - Pancer, Zeev
AU  - Pancer Z
FAU - Mariuzza, Roy A
AU  - Mariuzza RA
LA  - eng
SI  - PDB/3G39
SI  - PDB/3G3A
SI  - PDB/3G3B
GR  - R37 AI036900/AI/NIAID NIH HHS/United States
GR  - AI036900/AI/NIAID NIH HHS/United States
GR  - R01 AI047990/AI/NIAID NIH HHS/United States
GR  - R01 AI047990-09/AI/NIAID NIH HHS/United States
GR  - R37 AI036900-14/AI/NIAID NIH HHS/United States
GR  - AI065612/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090621
PL  - United States
TA  - Nat Struct Mol Biol
JT  - Nature structural & molecular biology
JID - 101186374
RN  - 0 (Antigens)
RN  - 0 (Leucine-Rich Repeat Proteins)
RN  - 0 (Ligands)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 3.2.1.- (hen egg lysozyme)
RN  - EC 3.2.1.17 (Muramidase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens/*chemistry/genetics/metabolism
MH  - Binding Sites
MH  - Chickens
MH  - *Lampreys
MH  - Leucine-Rich Repeat Proteins
MH  - Ligands
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Multiprotein Complexes/chemistry/metabolism
MH  - Muramidase/chemistry/genetics/immunology
MH  - *Protein Conformation
MH  - Proteins/*chemistry/genetics/*metabolism
MH  - Receptors, Cell Surface/*chemistry/genetics/metabolism
PMC - PMC2722044
MID - NIHMS117709
EDAT- 2009/06/23 09:00
MHDA- 2009/07/31 09:00
PMCR- 2010/01/01
CRDT- 2009/06/23 09:00
PHST- 2009/02/08 00:00 [received]
PHST- 2009/05/14 00:00 [accepted]
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/07/31 09:00 [medline]
PHST- 2010/01/01 00:00 [pmc-release]
AID - nsmb.1619 [pii]
AID - 10.1038/nsmb.1619 [doi]
PST - ppublish
SO  - Nat Struct Mol Biol. 2009 Jul;16(7):725-30. doi: 10.1038/nsmb.1619. Epub 2009 Jun 
      21.