PDBsum entry 3l89

Viral protein/protein binding

PDB id: 3l89

Contents

Protein chains

(+ 6 more) 183 a.a. *

(+ 6 more) 126 a.a. *

Ligands

NAG ×4

* Residue conservation analysis

PDB id:

3l89

Name:

Viral protein/protein binding

Title:

Human adenovirus type 21 knob in complex with domains scr1 and scr2 of cd46 (membrane cofactor protein, mcp)

Structure:

Fiber protein. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Fragment: ad21 fiber knob (unp residues 123-323). Engineered: yes. Membrane cofactor protein. Chain: m, n, o, p, q, r, s, t, u, v, w, x. Fragment: cd46 scr1 and scr2 domains (unp residues 35-160). Synonym: trophoblast leukocyte common antigen, tlx. Engineered: yes

Source:

Human adenovirus 21. Organism_taxid: 32608. Strain: 2145. Gene: 32608, l5. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

3.50Å R-factor: 0.206 R-free: 0.239

Authors:

K.Cupelli,T.Stehle

Key ref:

K.Cupelli et al. (2010). Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses. J Virol, 84, 3189-3200. PubMed id: 20071571

Date:

30-Dec-09 Release date: 14-Apr-10

Protein chains

Q2KS96  (Q2KS96_9ADEN) -  Fiber protein from Human adenovirus 21

Seq: 323 a.a.

Struc: 183 a.a.

Protein chains

P15529  (MCP_HUMAN) -  Membrane cofactor protein from Homo sapiens

Seq: 392 a.a.

Struc: 126 a.a.

J Virol 84:3189-3200 (2010)

PubMed id: 20071571

Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses.

K.Cupelli, S.Müller, B.D.Persson, M.Jost, N.Arnberg, T.Stehle.

ABSTRACT

The complement regulation protein CD46 is the primary attachment receptor for most species B adenoviruses (Ads). However, significant variability exists in sequence and structure among species B Ads in the CD46-binding regions, correlating with differences in affinity. Here, we report a structure-function analysis of the interaction of the species B Ad21 knob with the two N-terminal repeats SCR1 and SCR2 of CD46, CD46-D2. We have determined the structures of the Ad21 knob in its unliganded form as well as in complex with CD46-D2, and we compare the interactions with those observed for the Ad11 knob-CD46-D2 complex. Surface plasmon resonance measurements demonstrate that the affinity of Ad21 knobs for CD46-D2 is 22-fold lower than that of the Ad11 knob. The superposition of the Ad21 and Ad11 knob structures in complex with CD46-D2 reveals a substantially different binding mode, providing an explanation for the weaker binding affinity of the Ad21 knob for its receptor. A critical difference in both complex structures is that a key interaction point, the DG loop, protrudes more in the Ad21 knob than in the Ad11 knob. Therefore, the protruding DG loop does not allow CD46-D2 to approach the core of the Ad21 knob as closely as in the Ad11 knob-CD46-D2 complex. In addition, the engagement of CD46-D2 induces a conformational change in the DG loop in the Ad21 knob but not in the Ad11 knob. Our results contribute to a more profound understanding of the CD46-binding mechanism of species B Ads and have relevance for the design of more efficient gene delivery vectors.